Title of Invention

"PYROZOLO (1,5-ALPHA), PYRIMIDINYL COMPOUND"

Abstract

A pyrazolo (1,5-alpha), pyrimidinyl compound represented by the following structure: or a pharmaceutically acceptable salt, solvate, stereoisomer thereof, R1 is hydrogen; R2a and R2b are independently hydrogen or C1-C6 alkyl; Y is a direct bond or -C(R4aR4b)- where R4a and R4b are each hydrogen; Het is R5 is C1-C6 alkyl or C1-C6 haloalkyl; R6 at each occurrence is independently C1-C6 alkyl; n is 1; Ar is phenyl; R7 at each occurrence is C1-C6 alkyl or C1-C6 alkoxy; o is 2.

Full Text

PYRAZOLO (1,5-ALPHA) PYRIMIDINYL DERIVATIVES USEFUL AS CORTICOTROPIN-RELEASING FACTOR (CRF) RECEPTOR ANTAGONISTS CROSS REFERENCE TO RELATED APPLICATION This application claims the benefit of U.S. Provisional Application No. 60/620,060 filed October 19, 2004 and OB 0519957.5 field 30 September 2005, which is hereby incorporated by reference in iis entirety. TECHNICAL FIELD This invention relates generally to CRF receptor antagonists, and to methods of treating disorders by administration of such antagonists to a warm-blooded mammal in need thereof. BACKGROUND Or THE INVENTION The firsl conicatropin-releasing factor (CRF) was isolated from ovine hypothalami and identified as a 41-amino acid peptide (Vale et al., Science 273:1394- 1397, 1981). Subsequently, sequences of human and rat CRF were isolated and determined lo be identical but different from ovine CRF in 7 of the 41 amino acid residues (Riwier ei al., Proc. Natl. Acad. Sci. USA S0:4S5t, 1983; Shibahara et al.. EMBO J. 2:775, 1983). CRF has been found to produce profound alterations in endocrine, nervous and immanc system function. CRF is believed to be the major physiological regulator of the basal and stress-release of adrenocorticotropic hormone ("ACTH"), 6-endorphin, and other pro-apiomelanocortin ("POMC")-derived peptides from the anterior pituitary (Vale et al., Sconce 2/^:1394-1397, 1981). Briefly, CRF is believed to initiate its biological effects by binding to a plasma membrane receptor svhich has been found to be distributed throughout the brain (DeSouza et al., Science 224:1449-1451, 1984), pituitary (DeSouza el al., Methods Eniymol. J24:56Q, 1986; Wynn et al., Biochem. Biaphys. Res. Coinm. 7/0:602-608, 1983), adrenals (Udelsman et al., Nature 5/9:147-150. 1986) and spleen (Webster, E.L., and EB. DeSouza, Endocrinology 122:609-611, 1988). The CRF receptor is coupled to a GTP-binding protein (Perrin et al., Endocrinology 11& I 171-1179, 1986) which mediates CRF-sbmu!a!ed increase in intracelluiar production of cAMP (Bileicikjian, L.M , and \V.\V. Vale, Endocrinology 113'651-662, 1983). The receptor for CRF has now been cloned from rat (Perrin et al., Endo ^3(6):3058-3061, 1993), and human brain (Chen et al., PNAS 90(19):8967-8971, 1993; Vita et al., FEBS 335(1): 1-5, 1993). This receptor is a 415 amino acid protein comprising seven membrane spanning domains. A comparison of identity between rat and human sequences shows a high degree of homology (97%) at the amino acid level. In addition to its role in stimulating the production of ACTH and POMC, CRF is also believed to coordinate many of the endocrine, autonomic, and behavioral responses to stress, and may be involved in the pathophysiology of affective disorders. Moreover. CRF is believed to be a key intermediary in communication between the immune, central nervous, endocrine and cardiovascular systems (Crofford ei al., J. Clin. Invest 90:2555 2564, 1992; Sapolsky et al.. Science 238:522-524, 1987; Tilders et al., Regui Pcptides 5:77-84, 1982). Overall, CRF appears lo be one of the pivotal central nervous system neurotransmitters and plays a crucial role in integrating the body's overall response to stress. Administration of CRF directly to the brain elicits behavioral, physiological, and endocrine responses identical to those observed for a mammal exposed (o a stressful environment. For example, intracerebroventricular injection of CRF results in behavioral activation (Sutton et al., Nature 297:331, 1982), persistent activation of the electroencephalogram (Ehlers et al., Brain Res. 278:332, 1983), stimulation of the sympathoadrenomedullary pathway (Brown et al., Endocrinology 770:928, 1982), an increase of heart rate and blood pressure (Fisher et al., Endocrinology 110:2222, 1982), an increase in oxygen consumption (Brown et al.. Life Sciences 30:207, 1982), alteration of gastrointestinal activity (Williams el al., Am. J. Physiol. 253:0582, 1987), suppression of food consumption (Levine et al., Neuropbannacology 22:337, 1983), modification of sexual behavior (Sirinathsinghji et al., Nature 305:232, 1983), and immune function compromise (Irwin et al., Am. J. Physioi. 255:R744, 1988). Furthermore, clinical data suggests that CRF may be hypersecreted in the brain in depression, anxiety-related disorders, and anorexia nervosa. (DeSouza, Ann. Reports in Med. Chem. 25:215-223, 1990). Accordingly, clinical data suggests (hat CRF receptor antagonists may represent novel antidepressant and/or anxiolytic drugs that may be useful in the treatment of the neuropsychiatric disorders manifesting hypersecreiion of CRF. The first CRF receptor antagonists were peptides (see, e.g., Rwier et al., U.S. Patent No. 4,605,642; Rivier et ai.. Science 224:889, 1984). While (hese peptides established that CRF receptor antagonists can attenuate the pharmacological responses to CRF, peptide CRF receptor antagonists suffer from the usual drawbacks of peptide therapeutics including lack of stability and limited oral activity. CRF antagonists comprising compounds having a pyrazolo-[l,5a]- pyrimidine core are disclosed in the following patents and published applications: WO97291.09, US6313124, W09803510, WO9938868. WO9808847, JP2000038350, EPI097709 and US6664261, Further, this core is disclosed in application WO9535298 for analgesics, in application JP1010I672 for adenosine reinforcement agents, in application JP10101671 for nitrogen monooxide symhase inhibitors, in application W02001023387 for neuropeptide Yl antagonists, in application W02000044754 for fat accumulation inhibitors, and in application W02003101993 for hepatitis C virus replication inhibitors. Due to the physiological significance of CRF, the development of biologically-active small molecules having significant CRF receptor binding activity and which are capable of antagonizing the CRF receptor remains a desirable goal Such CRF receptor antagonists may be useful in the treatment of endocnne, psychiatric and neurological conditions or illnesses, including stress-related disorders in general. While significant strides have been made toward achieving CRF regulation through administration of CRF receptor antagonists, there remains a need in the art for effective small molecule CRF receptor antagonists. There is also a need for pharmaceutical compositions containing such CRF receptor antagonists, as well as methods relaung to the use thereof to treat, for example, stress-related disorders. The present invention fulfills these needs, and provides other related advantages. SUMMARY OF THE INVENTION This invention is generally directed to CRF receptor antagonists, and more specifically to CRF receptor antagonists having the following general structure (I): and pharmaceuucally acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein' RI is hydrogen, alky], substituted alky), haloalkyl, substituted haioalkyl. alkoxyalkyl, substituted alkoxyalkyl, arylaJkyI, substituted arylalkyl, heterocyclealkyl, or substituted heterocyclealkyl, Rja and Rib are independently hydrogen,C1-C6 alkyl, substituted C1-C6 alkyl.C1-C6 haloalkyl, substituted C1-C6 haloalkyl, arylalkyl. substituted arylalkyl, C1-C6 alkoxyalkyl, substituted C1-C6 alkoxyalkyl, alkylrulfonylalkyl, aminoaJkyl, monoalkylaminoalkyl or dialkyJaminoalkyl; or RI together with, the nitrogen to which it is attached and cither R^ or R2b together with the carbon to which R and R2b are attached form a 4-7 membered heterocyclic nng; or R2a and Rjb together with the carbon atom to which they are attached form a ring of 3-7 members optionally containing within the nng -O-, -S- or -NCRj)-; R2 is alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, acyl, -C(O)OR«, -C(0)NR,R,0l or S(0)2R,t; Y at each occurrence is independently a direct bond or -C(R m is 1 or 2, R2b and R2 independently hydroger C1-C6 alkyl, substituted C1-C6 alkyl, arylalkyl, substituted arylalkyl, C1-C6 alkoxyalkyi, substituted C1-C6 alkoxyalkyl, alkylsulfonylalkyl, aminoalkyl, monoalkylaminoalkyl or dialkylaminoalky); Or R4a and R5 together with the carbon atom to which they are attached form a ring of 3-7 members optionally containing within the ring -O-, -S- or -N(R3)-; Hetis or Rs is hydrogen, halogen,C1-C6alkyl, substituted C1-C6alkyl; C1-C6 alkoxy, substitutedC1-C6alkoxy, amino, alkyiamino or dialkylamino; R« at each occurrence is independently halogen, C1-C6 aJkyl or substituted C1-C6alkyl; n is an integer from 0-3 inclusive; Ar is phenyi or pyridyj; R7 at each occurrence is independently halogen, alky), substituted alkyl, Cr C1-C6alkoxy, substituted C1-C6alkoxy, -N^RoRio, alkylsulfonyl or substituted alkylsulfonyl; o is an integer from 0-3 inclusive; and each of Rg, R9, R(0 and RH is hydrogen, C1-C6 alkyl, substitutedC1-C6 alkyl, arylalkyl, substituted arylalkyl, C|-C6 alkoxyalkyl, substituted Ci-Q alkoxyalkyl, alkylsulfonylalkyl, aminoalkyl, monoalkylaminoalkyl or dialkylaminoalkyl. These and other aspects of the invention will be apparent upon reference to the following detailed description. To this end, various references are set forth herein which describe in more detail certain procedures, compounds and/or compositions, and are hereby incorporated by reference in their entirety. BRIEF DESCRIPTION OF THE FIGURES Figure 1 shows X-Ray powder diffraction data obtained for polymorph Form 1 of [3-(4- Methoxy-2-methyl-phenyl)-2,5-dirnethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-((S)-l-(3- methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine as described before. Form I is characterised by having an XRPD pattern with signals substantially as listed in Table 1. Figure 2 shows the Raman spectrum of polymorph Form 1 of [3-(4- Methoxy-2-methyl-phenyr)-2,5-dimethyl-pyrazolo(l,5-a]pyrimidiTi-7-yl}-[(S)-l-(3- methyI-[l,2(4]oxadiazol-5-yl)-propyl]-amine. Figure 3 shows a Differential Scanning Calorimetry (DSC) thermogram of polymorph Form i of [3-(4-Methoxy-2-methyl-phenyi)-2,5-dirnethyI-pyra2.olo[l,5- a]pyrimidin-7-y|)-[(S)-l-(3-methyl-(],2,41oxadiazo]-5-yl)-propy]]-am]rie. Figure 4 shows X-Ray powder diffraciion data obtained for polymorph Form 2 of [3-(4-Methoxy-2-meihyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]- [(S)-l-(3-methy]-[l,2,4]oxadiazol-5-yl)-propyl]-amine as described before. Form 1 is characterised by having an XRPD pattern with signals substantially as listed in Table 1. Figure 5 shows the Raman spectrum of polymorph Form 2 of [3-(4- Methoxy-2-[Tteihyl-phenyl)-2,5-dimethyl-pyTa2olo[l,5-a]pyrimidin-7-yl]-f(S)-l-(3- methyl-[ 1,2,4]oxadJazol-5-yl)-propyl]-amine. Figure 6 shows a Differential Scanning Calorimetry (DSC) thermogram of polymorph Form 2 of [3-(4-Methoxy-2-methyl-pheny])-215-dimcthyl-pyi-a2olo[l,5- a)pyrimidin-7-yl]-l(S)-l-(3-meihyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine. DETAILED DESCRIPTION OF THE UN VENTJON The present invention is directed generally to compounds useful as corticotropin-releasing factor (CRF) receptor antagonists. In a first embodiment, the CRF receptor antagonists of this invention have the following structure (I): and pharmaceutically acceptable salts, esters, soivates, stereaisomers and prodrugs thereof, wherein Ri is hydrogen, alky], substituted alkyl, haloalkyl, substituted habalkyl, alkoxyalkyl, substituted alfcoxyalkyl, arylalky), substituted arylalkyl, heterocyclealkyl, or substituted heterocyclealkyl; R2j and Rib are independently hydrogen, C1-C6 alkyl, substituted C1-C6 alkyl, Ci-Cs haloalkyl, substituted C1-C6 haloalkyl, arylalkyl, substituted arylalkyl,C1-C6 alkoxyalkyl. substituted C1-C6 alkoxyalkyl, alkylsulfonylalkyl, aminoalkyl, monoalkylaminoalkyl or dialkylaminoaikyl; or RI together with the nitrogen to which it is attached and either R2 or R2 together with Che carbon to which R2, and R3 are attached Form a 4-7 membered heterocycJic nng; or R2,and R2, together with the carbon atom to which they are attached form a nng of 3-7 members optionally containing within the ring -Q-, -S- or -N(R3)-; RS is alky], substituted alkyl, arylalkyl, substituted arylalkyl, acyl, -C(0)OR8, -C(O)NR9R,0, orS(O)2Rn; Y ai each occurrence is independently a direct bond or -C(R4aRjb)m-; m is 1 or 2; R.U and R4b are independently hydrogen, Ct-C6 alkyl, substituted C)-Q, alkyl, arylalkyl, substituted arylalkyl, Ci-C« alkoxyalkyl, substituted Ci-Q alkoxyalkyl, alkylsulfonylalkyl, aminoalkyl. monoalkylaminoalkyl or dialkylaminoaikyl; or R4» and Rtt, together with the carbon atom to which they are attached form a ring of 3-7 members optionally containing within the ring -O-, -S- or -N(Rj)-; Het is (Figure Removed) Rs is hydrogen, halogen, C1-C6 alkyl, substituted C1-C6 atkyl, C1-C6 alkoxy, substituted C1-C6alkoxy, amino, alkylamino or dialkylamino; RS at each occurrence is independently halogen, C1-C6 alkyl or substituted C1-C6 alkyl; n is an integer from 0-3 inclusive; Ar is phenyl or pyridyl; R? at each occurrence is independently halogen, alkyl, substituted alkyl, C1-C6 C1-C6alkoxy, substituted C1-C6alkoxy, -NR9R10, alkylsulfonyl or substituted alkylsulfonyl; o is an integer from 0-3 inclusive; and each of R$, RQ, RIO and RH is hydrogen, C1-C6 alkyl, substituted C1-C6 alkyl, arylalkyl, substituted arylalkyl, C1-C6 alkoxyalkyl, substituted C1-C6 alkoxyalkyl, alkylsulfonylalkyl, aminoalkyl, rnonoalkylaminoalkyl or dialkylamtnoalkyl. The CRF receptor antagonists of this invention have utility over a wide range of therapeutic applications, and may be used to treat a variety of disorders or illnesses, including stress-related disorders. Such methods include administering an effective amount of a CRF receptor antagonist of this invention, preferably in ihe form of a pharmaceutical composition, to a mammal in need thereof. Accordingly, in another embodiment, pharmaceutical compositions are disclosed containing one or more CRF receptor antagonists of this invention in combination with a pharmaceutically acceptable carrier and/or diluent. As used herein, the above terms have the following meaning: 'Alkyl" means a straight chain or branched, noncyclic or cyclic, unsaturated or saturated aliphatic hydrocarbon containing from 1 to 10 carbon atoms, while the terms "lower alkyl" and "C|-Ce alkyl" have the same meaning as alkyl but contain i to 6 carbon atoms. Representative saturated straight chain alkyls include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, and the like; while saturated branched alkyls include isopropyl, .sec-butyl, isobutyl, fcrr-butyl, isopentyl, and the like. Representative saturated cyclic alkyls include cyclopropyl, cyclobutyl, cyclopentyl. cyclohexyl, -CHjcyclopropyl, -CHj-cyclobutyl, -CFh-cyclopentyi, -CHj-cyclohexyl, and the like; while unsaturated cyclic alkyls include cyclopentenyl and cyclohexenyl, and the like. Cyclic alkyls. also referred to as "hornocyclic rings," include di- and poly-homocyclic rings such as decalin and adamantyl. Unsaturated alkyls contain at least one double or triple bond between adjacent carbon atoms (referred to as an "alkenyl" or "alkynyl". respectively). Representative straight chain and branched alkenyls include ethylenyl, propylenyl, 1- butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3-methyl-l-butenyl, 2-methyl-2- butenyl, 2,3-dirnethyl-2-butenyl, and the like; while representative straight chain and branched alkynyls include acetylenyl, propynyl, I-butynyl, 2-bu;ynyl, 1-pentynyl, 2- pentynyl, 3-methyM butynyl, and the like. "Aryl" means an aromatic carbocyclic moiety such as phenyl or napruhy). "Arylalkyl" means an alkyl having at least one alky) hydrogen acorn replaced with an aryl moiety, such as benzyl (i.e., -CHi-phenyl), -CHz-(l- or 2-naphthyl), -(CHiiaphenyl, -(CH2)3phenyl, -CH(phenyl)2, and the like. "Heteroaryr means an aromatic heterocycle ring of 5- to 10-members and having at least one heteroatom selected from nitrogen, oxygen and sulfur, and containing at least 1 carbon atom, including both mono- and bicyclic ring systems. Representative heteroaryls include (but are not limited to) furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrrolyl, indolyl, isoindolyl, azaindolyl, pyridyl, quinolinyl, isoquinolinyl, oxazolyl, isooxazolyl, benzoxazolyl, pyrazolyl, imidazolyl, beniimidazolyl, ihia/olyl. benzothiazoly), isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl, quinazolinyl and oxadiazolyl, "HeteroarylaJkyl" means an alkyl having at least one alkyl hydrogen atom replaced with a heteroaryl ipoiety, such as -CHj-pyridinyl, -CHj-pyrimidinyl, and the like. "Heterocycle" (also referred to herein as a "heterocycle ring") means a 5- to 7-membered monocyclic, or 7- to 14-membered polycyclic, heterocycle ring which is either saturated, unsaturatfid or aromatic, and which contains from 1 to 4 heteroatoms independently selected frotn nitrogen, oxygen and sulfur, and wherein the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quatemized, including bicyclic rings in which any of the above heterocycles are fused to a benzene ring as well as tricyclic (and higher) heterocycle rings. The heterocycle may be attached via any heteroalom or carbon atom. Heterocycles include heteroaryls as defined above Thus, in addition to the aromatic heteroaryls listed above, heterocycles also include (but are not limited to) rnorpholinyl, pyrrolldinonyl, pyrrolidinyl, piperidinyl, piperizinyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, letrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydroprimidinyl, tetrahydrothiopheny], tetrahydrothiopyranyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, tetrahydrothiopyrany), and the like. "Heterocyclealkyl" means an alkyl having at least one alkyl hydrogen atom replaced with a heterocycle, such as -CHi-morphoIinyl, and the like. "Haioalkyl" means an a l k y l group having at least one alkyl hydrogen atom replaced with a halogen, such as CH2CI, CHC12, CCIj, CH2F, CFj, and the like. "C,-C6 haloalkyl" has the same definition as 'hatoalkyl" but contains 1 to 6 carbon atoms. The term "substituted" as used herein means that at least one hydrogen atom on any of the groups described herein (e.g., alkyl, alkoxy, alkoxyalkyl, aryl, arylalkyt, heteroaryl, heteroarylalkyl, heterocycle or heterocyclealkyl) is replaced with a substituent. In the case of an oxo substituent ("(=O)") two" hydrogen atoms are replaced. "Substituents" within the context of this invention include halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, aJkyl, substituted alkyl, alkoxy, thioalkyl, haloalky), hydroxyalkyl, alkoxyalkyl, haloalkoxy, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroary), substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycle, substituted hcterocycle, heterocyclealkyl, substituted heterocyclealky), -NRaRb, -NR,C(=0)Rbl -NR4C(=0)NR3Rb, -NR,C(=0)ORb -NRaSO2Rb, -OR,. -C(=0)Ra -C(=0)OR3, .C(=0)NR,Rb. -OC(=0)NR3Rb, -SH, -SR,, -S(=O)Ra, -S(=O)jR.. -OS(=O)2R4, -S(=O)2ORi, wherein R3and Rbare the same or different and independently hydrogen, alkyl, haloalkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocycle. substituted heterocycle, heterocyclealkyl or substituted heierocyclealkyl. "Halogen" means fluoro, chloro, bromo or iodo. "Alkoxy" means an alky! moiety attached through an oxygen bridge (i.e., -O-alkyl) such as -C1-C6ethyl, -O-ethyl, and the like. C1-C6 alkoxy1" has the same definition as aikoxy but contains I to 6 carbon atoms. "Haloalkoxy" means an alkoxy having at least one hydrogen atom replaced with halogen, such as trifluoromethoxy and the like. "Alkoxyalkyl" means an alkyl having at least one hydrogen atom replaced with alkoxy, such as methoxymethyl and the like.C1-C6 alkoxyalkyl" has the same definition as "alkoxyalkyl" where the alkoxy group has 1 to 6 carbon atoms. 'Thioalkyl" means an alkyl moiety attached through a sulfur bridge (i.e., -S-atkyl) such as -S-methyl, -S-ethyl, and the like. "Alkylamino" and "dialkylamino" mean one or two alkyl moieties attached through a nitrogen bridge (i.e., -NHalkyl or -N(alky!)(alky])) such as methylamino, ethylamino, dimethylamino, dieihylammo, and the like. "Hydro*yalkyl" means an alkyl substituted with at least one hydroxyl group. "Mono- or di(cycloalkyl)methyr represents a methyl group substituted with one or two cycloalkyl groups, such as cyclopropylmethyl, dicydopropylmethyl, and the like. "Alkylcarbonylalkyl" represents an alkyl substituted with a -C(=O)alkyl group. "Alkylcarbonyloxyalkyl" represents an alkyl substituted with a -C(=O)Oalkyl group or a -OC(=0)alkyl group. "Alkylthioalkyl" represents a alkyl substituted with a -S-alkyl group. "Mono- or di(alkyl)aminoalkyl" represents an alkyl substituted with a mono- or di(alkyl)amino. "Acyl" represents alky)~C(=O)-. Embodiments of the invention presented herein are for purposes of example and not for purposes of lirrjitation. In one embodiment of this invention, RI may represent hydrogen, alkyl, substituted alkyl, haloalkyl, substituted haloalkyl, alkoxyalkyl, substituted alkoxyalkyl, arylalkyl, substituted arylalkyl, helerocyclealkyt, or substituted heterocyclealkyl. Thus, representative compounds of this invention include, for example, the following structure (Ha) where RI is hydrogen, structure (lib) where RI is methyl, structure (He) where RI is methoxyrnethyl, structure (lid) where RI is benzyl, and structure (He) where RI is pyrid-2-yl-methyl: (Figure Removed) Fn funher embodiments of the invention, Rja and Rzb are independently hydrogen, C1-C6 alky], substituted C1-C6 alkyl, C1-C6 haloajkyl, substituted C1-C6 haloalkyl, arylalkyl, substituted arylalkyl, C1-C6 alkoxyalkyl, substituted C1-C6 alkoxyalkyl, alkylsulfonylalkyl, arrunoalkyl, monoalkylaminoalkyl or dialkylaminoalkyl. Thus, representative compounds of this invention include the following structure (Ilia) where Ria and Rjb are hydrogen. Further representative compounds wherein RX, is hydrogen include structure (Hlb) where R2, is alky] exemplified by methyl, structure (Ilic) where R^ is arylalkyl exemplified by benzyl, structure (Hid) where R2a is alkoxyalkyl exemplified by methoxymethyl, stnjcture (lUe) where RI, is alkylsulfonylalkyl exemplified by melhylsulfonylmethyl, and structure (Itlf) where R& is aminoalkyl exemplified by aminomethyl. (Figure Removed) In further embodiments of ihe invention, Rt together with the nitrogen to which it is attached and either R^ or Rib together with the carbon to which Rja and R2b are attached form a 4-7 membered heterocyclic ring exemplified in structure (IVa) as the 7- pyrrolidin-l-yl-pyrazolo[l,5-a]pyrimidine and in structure (IVb) as the 7-pipendin-J-ylpyrazolo[ l,5-a]pynmidine. (IVa) (IVb) In further embodiments of the invention, R2a and R2b together with the carbon atom to which they are altached form a ring of 3-7 members exempticd by cyclopropyl in the following structure (Va) and by ring "A" in ihe following structure (Vb) wherein ring "A" optionally contains -0-, -S- or -N(Rj)- and Rj is alkyl, substituted alkyl, aryaltcyl, substituted arylalkyl, acyl, -C(O)ORg, -C(0)NR9Rio, or S(O)2Rns~A (Figure Removed) In further embodiments of the invention, Y at each occurrence is independently a direct bond or -QR1R1m-, where in is 1-2 inclusive and R4a and R2b are independently hydrogen, C1-C6 alkyl, substituted C1-C6 alkyl, arylalicyl, substituted arylalkyl, C1-C6alkoxyalkyl, subslituted C1-C6 alkoxyalkyl, alkylsulfonylalkyl. aminoalkyl, rnonoalkylaminoalkyl ordialkylaminoalkyl. Thus, representative compounds of ihis invention include for example the following structure (Via) when Y is a direct bond and structure (VIb) when Y is -C(R*,R4b) ,n-.and m is 1. (Figure Removed) In another embodiment of the invention, R2 and R4b together with the carbon atom to whjch they are attached form a ring of 3-7 members optionally containing within the ring -0-, -S- or -N(Rj)-. Thus, representative compounds of this invention include for example the following structure (Vila) when R4a and R4b together with the carbon atom to which they are attached form a cyclopropyl ring, and structure (VITb) when Rja and Rtb together with the carbon atom to which they are attached form ring "B" wherein ring "B" optionally contains -0-, -S- or -N(R3>-. (Vila) (VUb) In another embodiment of the invention, Het is one of three oxadiazoles exemplified in the following structures (Vllla)-(VIIIc) wherein R5 is hydrogen, halogen, C1-C6 alkyl, substitutedC1-C6 alkyl, C1-C6 alkoxy, substituted C1-C6 alkoxy, amjno, alkylamino or dialkylamino. (Villa) (VHIb) (VIlTc) [n another embodiment of the invention, R6 at each occurrence is independently independently halogen,C1-C6 alkyl or substituted C1-C6 alkyl, and n is 0-3 inclusive. Thus, representative compounds of this invention include for example the following structures (IXa - Kh) wherein R« independently occupies all possible combinations of positions 2,;5 and 6 of the pyrazolo-[I,5a]-pyrimidines core: (Figure Removed) In another embodiment of the invention, Ar is phenyl or pyridyl, RT at each occurrence is independently halogen, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6alkoxy, substituted C1-C6 alkoxy, -NRoRio. alkylsulfonyl or substituted alkylsulfonyl, and o is 0-3 inclusive. Thus, representative compounds of the invention include for example the following structure (Xa) when Ar is phenyl and structure (Xb) when Ar is pyridyl. (Figure Removed) Compounds of the present invention include: [l-(3-Cyclopropyl-(l,2 2,5-dimelhyl-pyra2olo[l,5-a3pyrimJdin-7-yl]-amjne (Ex. 11-1); [l-(3-Isopropyl-[I,2,4]oxadia2o!-5-yl)-propyl]-[3-(4-methoxy-2-methylphenyl)- 2,5-dirnethyl-pyrazo]o(l,5-a]pyrimidin-7-yl]-amine(Ex. 11-2); [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazo]o[l,5-a]pyrimidin-7- yl]-[l-(3-methyl-[i,2,4]oxadiazol-5-yl)-2-phenyl-ethyl]-amine (Ex. 11-3); (l-(3-lsopropyl-[l,2.4]oxadiazol-5-yl)-propyl]-[3-(4-methox.y-2-methylphcnyl)- 2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl)-arnine (Ex. Jl-4); [3-(4-Methoxy-2-methyl-phenyl)-2,5-dirnethyl-pyrazolo[l,5-a]pyrimidin-7- yl]-[l-(3-methyl-[l,2,4]oxadiazol-5-yl)-butyl]-amine(Ex. 11-5); (3-(4-Methoxy-2-mcthyl-pheny!)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7- yl]-(3 methyl-fl,2,4]oxadiazol-5-ylniethyl)-amine (Ex. 11-6); (3-Cyclopropyi-[i,2,4]oxadiazol-5-ylmeihyl)-[3-(4-methoxy-2-meihylphenyl)- 2,5-dimethy]-pyrazo)o[l,5-a]pyrimidin-7-yJ]-amine (Ex, 11-7); (3-Isopropyl-[l,2,4]oxadiazol-5-ylmethy])-[3-(4-methoxy-2-methylpheny))- 2,5-dnneihy]-pyrazolo[l,5-a]pyrimidin-7-yi]-amine (Ex. 11-8); [2-(3-Cyclopropyl-[1.2,4]oxadiazol-5-yl)-(R)-]-methyl-ethyI]-[3-(4- methoxy^-methyl-phenyO.S-dimcihyl-pyrazolofl.S-alpyrimidin-l-yll-amine (Ex. 11- 9); [3-(4-Methoxy-2-mcthyl-phenyl)-2,5-diniethyl-pyrazolo[l,5-a]pyTimidin-7- y]]-[(R)-l-methyl-2-(3-methyl-[l,2,4]oxadiazol-5-yl)-ethyl]-amine(Ex. 11-10); [3-(4-Me(hoxy-2-inethyl-phenyl)-2,5-dimcthyl-pyrazo]o[l>5-a]pyrimidin-7- yl]-(l-(3-mfluoromeihyl-[L,2,4]oxadia2ol-S-yl)-propyl]-amine(Ex. 11-11); (l-(3-Cyc]opropyI-[l,2,4]oxadiazol-5-yI)-cyclopropy]]-[3-(4-meihoxy-2- methy|-phenyl)-2,5-dimethyl-pyra2olo[l,5-a]pyrimidin-7-y]]-amine (Ex. 11-12), P-(4-Methoxy-2-methy|-phenyl)-2,5-dimethyl-pyrazolo(l,5-a]pyrimidin-7- yl3-[l-(3-me(hy!-[l,2,4]oxadiazoI-5-yl)-cyclopropyt]-amine (Ex. 11-13); [l-(3 Ethyl-{l,2,41oxadiazol-5-yl)-cyclopropylH3-(4-methoxy-2-methylpheny])- 2,5-dimethyl-pyrazolo(l,5-a]pyrimidin-7-yl]-amine (Ex. 11-14); [ 3-(4-Methoxy-2-methyl -phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7- yl]-(3-propyl-[ l,2,4)oxacjia2ol-5-ylmethyl)-aniine (Ex. 11-15); {3-(4-Mftthoixy-2-methyl-phenyl)-2,5-dimethyI-pyra2olo[l,5-a]pyrimidin-7- yl]-tl-(3-trifluoromethyl-[l,2,4]oxadia2ol-5-yl)-cyclopropyI]-amine (Ex. IL-16); 12-(3-Ethyl-tl,2.4]oxadia2ol-5-yl)-(R)-l-methyl-ethyl]-[3-(4-methoxy-2- mcthyl-phenyl)-2,5-dimelhyl-pyrazolo[!,5-a]pyrimidm-7-yl]-aminc (Ex. 11-17); |3-(6-Dimethylaraino-4-rnethyl-pyridin-3-y])-2,5-dimethyl-pyrazo!o[l,5- a]pyrimidin-7-yI)-[3-methyl-(R)-l-(3-methyl-{l,2,4]oxadiazol-5-yl)-butyl]-amJne (Ex. 11- 18); 3-(2,4-Dimcjthoxy-phenyl)-2,5-dimethyl-7-[{S)-2-(3-mechyl- [l^^Joxadiazol-S-yO-pyirolidin-l-ylJ-pyrazolofl.S-alpyrimidine (Ex. 11-19); (3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolotl,5-a]pyrimid)n-7-yl]- [l-(3-methyl-{ 1,2,4]oxadia*ol-5-yl)-propyl]-amine (Ex. 11-20); |3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyra2olo(l,5-a]pyn'midin-7-y]]- [l-(3-methy]-[l,2,4]oxadia2ol-5-yl)-ethyl]-amine (Ex. 11-21); [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[lv5-a]pyrimJdin-7-yl]- [l-(3-methyl-[ 1,2,4]oxadiazo!-5-yl)-butyl]-aminc (Ex. 11-22); [3-(2,4-Dimethoxy-phenyl)-2,5-dimethy]-pyrazolo(l,5-a]pyrimidin-7-y!]- I3-rnethyl-l-(3-methyl-n,2,4]oxadiazol-5-yl)-butyl)-amine (Ex. 11-23); |3-(2,4-Dimcthoxy-phenyl)-2,5-dimethyl-pyra2olo[l,5-a]pyriniidin-7-y!]- methyl-(3-methyl-fl,2,4]ox,adiazol-5-ylmethyl)-amine(Ex. 11-24); Benzyl-[3-(6-dimethylamino-4-methyl-pyridia-3-yl)-2,5-dimcihylpyrazo) o(l,5-a]pyrimidin-7-ylJ-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-amine (Ex. 11- 25); p-(4_IVIethoxy-2-methyl-phenyl)-2,5-dimethyl-pyra2olo(l,5-a]pyrirriidin-7- yl]-[l-(3-methyl-[l,2,4)oxadiazol-5-yl)-propyn-amine(Ex. 11-26); (3-(4-iVfethoxy-2-meihyl-phenyl)-2,5-diroeihyl-pyrazolo(I,5-a]pyriniidin-7- yt]-[l-methyl-2-(3-rnelhyl-ll,2,4]oxadiazol-5-yl)-ethyl]-amine(Ex. 12-1); Benzyl-[3^(4-!nethoxy-2-mcihyl-phenyl)-2,5-dimethyl-pyra2olo[l,5- a]pynmidin-7-y|]-(3-methyl-[i,2,4]oxadiazol-5-yliT\ethyl)-amirie (Ex. 12-2); (3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimJdin-7- yl] [2,2,2-trifluoro-l-(3-meihyI-[i,2,4]oxadiazol-5-ylmethyl)-ethyl]-amine(Ex. 12-3); (2-(3-Cycloprapyl-[l,2,41oxadia2ol-5-yl)-l-mechyl-cthyl]-[3-(4-niethaxy- 2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a3pynmidin-7-yl]-amine (Ex. 12-4); [2-(3-Isopropyl-[l>214joxadiazol-5-y!)-l-methyl-ethyl]-[3-(4-methoxy-2- mcthyl-phenyl)-2,5-dimethy1-pyrazolo[i,5-a]pyrimidin-7-yl]-amne(Ex. 12-5); [2-(3-Cyclopropyl-[l,2,4]oxadiazol-5-yl)-(S)-l-rnethyl-ethyl]-[3-(4- nnethoxy-2-methyl-phcnyl)-2,5-dimethyl-pyra2olo[l,5-a]pyTirnidin-7-yl]-ainine (Ex. 12- 6); [2-(3-Isopropyl-[l,2,4]oxadiazol-5-ylHS)-l-methyl-ethyl]-[3-(4-mechoxy- 2-methy!-phenyl)-2,5-dimeihyl-pyrazolo[l ,5-a)pyiiinidin-7-y]]-amine (Ex. 12-7); (3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyraz.olo(J,5-a]pyiimidin-7- yl]-[(S)-l-tneihyl-2-(3-meihyl-[l,2,4]oxadiazol-5-yl)-ethyl]-amine(Ex. 12-8); [3-(4-Me(hoxy-2-methyl-phenyl)-2,5-dimcihyl-pyrazolo[l,5-a]pyrimidin-7- yl)-[l-(3-methyl-[l,2,4]oxadiazol-5-ylmethy1)-pTOpyl]-amine (Ex. 12-9); [t-(3-CyclopropyI-[l,2,4]oxadiazol-5-y]methy[)-propyl]-[3-(2,4- dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-amine(Ex. 12-10); P-(2,4-Dimethoxy-phenyI)-2,5-dimethyl-pyra2olo[1.5-a]pyrimidin-7-yl]- [l-(3-methyl-[i,2,4]oxadia2ol-5-ylmethyl)-propyI]-amine(Ex. 12-11); |?-(4-Methoxy-2-methyl-phenyl)-2,5-dimtthyl-pyrazo]o[L,5-a]pyrimidin-7- yl]-[(S)-l-(3-mclhyl-[l,2,4)oxadiazo!-5-yl)-buty)]-amine(Ex. 13-1); [3-(4-Melhoxy-2-rnethyl-pheny!)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7- y!]-(2,2,2-tnnuoro-(S)-l-(3-methyl-[l,2,4]oxadia2ol-5-ylinethyl)-ethyl]-amiTie(Ex. 13-2); |3-(4-Methoxy-2-methyl-phcnyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7- yl)-[l-methyi-2-(3-trifluoromethyl-[l,2,4]oxadiazol-5-yl)-ethyl]-amine (Ex. 13-3); [3-(2-Ch)oro-4-melhoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyriniidin-7- yl]-[2,2,2-trifluoro-(S)-l-(3-methy]-[l,2.4]oxadiazol-5-ylmcthyI)-ethyl]-amine(Ex. 13-4); [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyra2o)o[!,5-a]pyrimidin-7- y]]-[(R)-l-meLhyI-2-(3-trif]uoromethyl-(l,2,4]oxadia2ol-5-yi)-ethyl]-amine(Ex. 13-5); (3-(2-Chloro-4-methoxy-phenyl)-2,5-dimethyl-pyrazolo[I,5-a)pyrimidin-?- yl]-[(R)-l-methyl-2-(3-trifluoromethyl-[l,2,4]oxadiazol-5-yl)-ethy]]-amine(Ex. 13-6); (3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pynmidin-7-y!]- [(R)-l-methyl-2-(3-tnnuoromethyl-[l,2,4]oxadiazol-5-yl)-«[hyl)-amine(Ex. 13-7), [3-(2,4-Dimcthoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pynmidin-7-yl]- [2,2,2-trif1uoro-(S)-l-(3-methyI-[l,2,4)oxadiazo]-5-yimethyl)-ethyI]-amine(Ex. 13-8); [3-(2,4-Dimdthoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pynnnidin-7-yl]- [2,2,2-trifluoro-(S)-l-(3-trifHuoromethyl-[l,2,4]oxadiazol-5-y)methy))-ethyl]-amine (Ex. 13-9); l3-(4-Methoxy-2-methyl-phenyI)-2,5-dimethyl-pyrazolo[l,5-a)pyrirrudin-7- yl]-[(S)-l-(3-methy]-[l,2,4]bxadiazoI-5-yl)-propyl]-amineCEx. 14-1); [3-(4-Methoxy-2-roethyl-phenyl)-2>5-dimethyl-pyra2olo[l,5-a]pyrimJdin-7- yl]-[(R)-l-(3-methy]-[l,2,4}oxadiazo]-5-yl)-propyl]-amine(Ex. 14-2); 3-(4-Methox;y-2-methyl-phenyl)-2,5-dimethyl-7-[(S)-2-(3-methyl- [1,2,4]oxadia2oi-5-ylmelhyi)-pyrrolidin-l-yl]-pyrazolo[l,5-a}pyrimJdjne (Ex. 14-3); [S^-ChlorcMt-methoxy-phenyO^.S-dimethyl-pyrazolofl.S-aJpynmidin-?- yl]-[(S)-l-(3-methyl-(ll2,4]&xadiazoI-5-yl)-propyl]-amine(Ex. 14-4); (3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a|pyrimidin-7-y]]- (2-methoxy-ethyl)-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-amine (Ex. 15-1); (5-|2,5-Dimethyl-7-[(S)-2-(3-methyH1.2,4]oxadiazol-5-yl)-Pyrrolidin-lyl]- pyrazo)o[l ,5-a]pyrimidin-3-yl)-4-methyl-pyridin-2-yI)-dimethyl-aniine (Ex. 15-2); [3-(6-Dimethylamino-4-methyl-pyridin-3-yI)-2,5-dimethyl-pyrazolo[l,5- a]pyTimidin-7-yl]-(2-roethoKy-ethyl)-(3-methyl-[l,2,4)oxadiazol-5-ylmcthyl)-arnine (Ex. 15-3); [3-(4-Ethoxy-phenyl)-2,5-dimelhy]-pyra20Jo[L,5-a]pyrirnidin-7-yl}-(2- methoxy-ethyl)-(3-methyl-{l,2>4]oxadiazol-5-ylmethyl)-amine(Ex. 15-4); f3-(2 (2-methoxy-ethyl)-[3-(3-methyI-[l ,2,4]oxadiazol-5-yl)-propyl]-amine (Ex. 16-1); [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l15-a]pyrimidin-7- yl]-((R)-1 -mcthy!-2-(5-methyl-[ 1,2,4]oxadia2ol-3-yl)-ethyl]-amine (Ex. 17-1); ,!3-(4-Mclhoxy-2-methy!-phenyl)-2,5-dimethyl-pyTa20]o[].5-alpyrimidin-7- yl]-[(S)-l-(-^-methyl-[J,2l4)o.\adia20]-3-y]meihy])-propy)3-aminc(Ex. 17-2), [3-(4-Methoxy-2-methy]-pheny1)-215-dJmeihy)-pyrazolo(J,5-a]pynmJdin-7- ylJ-[(JD-l-(5-methyl-[J,2,4]oxadiazol-3-y]methyl)-propylJ-amine(Ex. 17-3); (3-(4-Methoxy-2-methyl-phenyl)-2,5-dime(hy!-pyra2o]o[l,5-a)pynmidin-7- yl]-[(S)-l-mcthyl-2-(5-methyi-[l,2.4]oxadiazol-3-yl)-ethyl]-amine(Ex. 17-4); ((R)-2-(5-CyclopropyI-ti>2,4]oxadiazol-3-yl)-l-methyl-6thyl]-[3-(4^ me{hoxy-2-methyl-phenyl)-2,S-dimethyl-pyrazolo[l,5-a]pyrimidJn-7-yl]-amine (Ex, 18- i); [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrirnidin-7- yl]-[(R)-l-mcthy]-2-(5-(rinuoromethyl-[l,2,4]oxadia2ol-3-yl)-ethyl]-amJni(Ex. 18-2); [3-(4-Methoxy-2-meihyl-phenyl)-2,5-dinnethyl-pyrazolo[l)5-a]pyrim)din-7- yi]-t(S)-2;2,2-tnfluoro-l-(5-Fneihyl-[l,2,4]oxadia2o]-3-ylmcthyl)-ethyl]-amine(Ex. 19-1); Eihyl-[3-(4-methoxy-2-meihyl-phenyl)-2,5-dimethyl-pyrdzolo(l,5- a]pyrimidm-7 yl]-(3-mcihyl-fl,2,4]oxadiazoi-5-ylmethyl)-amine (Ex. 20-1); 3-(4-Meihoxy-2-meihyl-phenyl)-2,5-dimeihyl-7-(2-(3-methyl- [!,2.4]oxadiazol-5-ylmethyl)-piperidin-l-yl]-pyrazolo[l,5-a]pyrimtdine(Ex. 20-2); [3-(4-Melhoxy-2-methyl-phcnyl)-2,5-dimethyl-pyra2olo[l,5-a]pyrimJdin-7- ylHl-fl^^loxadiazol^-yl-propyO-amine (Ex. 21-1); [3-(4-Methoxy-2-inelhyt-pheny])-2,5-dimerhy!-pyrazolo[l,5-a]pyrimidin-7- yl]-{l-(5-rnethyl-fl,3,4]oxadiazol-2-yl)-propyl]-ammc(Ex. 22-1); [3-(4-Methoxy-2-methyI-phenyl)-2,5-dimcthyl-pyrazx)lo[l,5-a]pyrimidin-7' y!]-[l-methyl-2-(5-meihyl-[l,3,4]oxadiazol-2-yi)-ethyn-aminft(Ex. 23-1); (B-fA-Methoxy^-methyl-phenyO-l.S-dimethyl-pyrazolotl.S^pyriniidin-?- yl]-[!-meihyl-2-(5-irif]uoromelhyI-[J>3,43oxadia201-2-y!)-cthyl]-amine(Ex. 23-2); f3-(2-Ch)oro4-mcthoxy-phtnyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7- yl)-[l-(3-merhy]-[l,2,4]oxadiazol-5-yl)-propyl]-amine (Ex. 24-1); f3-(4-Chloro-2-methoxy-phenyl)-2,5-dimethyl-pyra2olo[l,5-a]pynmidin-7- yf]-fi-(3-methyi-[l>2,4]oxadia2ol-5-yl)-propy!]-amine(Ex, 24-2); yl]-[l-(3-methyl-(l,2,4)oxadiazo]-5-y!)-propyl]-amine (Ex. 24-3); f3-(4-Chloro-2-mcthyl-phenyf)-2,5-dimeihyl-pyrazolo[I15-a}pyrimidin-7- yl]-[l-(3-methy)-n,2.4Joxadia2ot-5-yl)-propylJ-amine(Ex. 24-4); [ 3-(2-Chloro-4-trifluoromeihy l-phenyl}-2,5-dimethyl-pyrazolo[ 1,5- a]pyrimidin-7-y!]-[l (3-methyl-[l,2,4Joxadta2ol-5-yl)-propy!]-amine (Ex. 24-5); and f3-(2-Chtoro-4-methyl-phenyJ)-2,5-dimethy]-pyrazolo(J,5-a)pyrimidJn-7- y)]-|l-(3-meihy]-[l,2.4Joxadiazol-5-yl)-propyJ]-amine(Ex. 24-6). tn another embodiment of the present invention, polymorphs of [3-(4- Methoxy-2-methyl-phenyl)-2,5-dimethyI-pyra2oIo[l,5-aJpyrimidin-7-yl)-{(S)-l-(3- rnethyl-n^^Joxadiazol-S-yO-propylJ-arnJne (Example 14-1) are reported. Polymorph Form 1 exhibits a predominant endotherm peak at about 1083 °C and exhibits a X-ray powder diffraction spectrum as shown in Figure 1. The X-ray powder diffraction pattern of polymorph Form I as shown in Figure 1 exhibits predominant peaks (expressed in degrees 2(9 (+/- 0.15 degrees 26) at one or more of the following positions: 6.721, 11.757, 13.323, 18.222, 21.426 and 21.974. More specifically, such characteristic peaks are at 11.757 and 21.974, and further at 6.721 and further at 13,323, 18,222, and 21.426. Polymorph Form 2 exhibits a predominant endotherm peak at about 115.1 °C as shown in Figure 6 and exhibits a X-ray powder diffraction spectrum having peaks as shown as shown in Figure 4. In another embodiment, [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethylpyrazolotl. 5-a]pyrimidin-7-yl3-[(S)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amin£ is in the form of a composition or mixture of polymorph Form 1 along with one or more other crystalline, solvate, amorphous, or other forms. More specifically, the composition may comprise from trace amounts up to 100% polymorph Form 1, or any amount in between - for example, the composition may comprise less than 0.1%, 0.5%, 1%, 2%, 5%, 10%, 20%, 30%, 40% or 50% by weight of polymorph Form 1 based on the total amount of [3-(4-Methoxy-2-rnethyl-phenyl)-2,5-dimethyi-pyra2olo[l,5-a]pynmidin-7-yl]-((S)-l- (3-methyl-[l,2,4]oxadiazo>5-yt)-propyl|-amine in the composition. Alternatively, the composition may comprise at least 50%, 60%, 70%, 80%, 90%, 95%, 97%, 98%. 99%, 99.5% or 99.9% by weight of polymorph Form 1 based on the total amount of [3-(4- Me.thoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-l-(3 methyl-[l,2,4)oxadia2ol-5-yl)-propyl]-amme in the composition. In another embodiment, [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethylpyrazo] o[l,5-alpynmidin-7-yl]-f-:S)-l-(3-methyl-[l,2,4]oxadia2o)-5-yl)-propyl]-amine is in the form of a composition or mixture of polymorph Form 2 along with one or more other crystalline, solvate, amorphous, or other forms. More specifically, the composition may comprise from trace amounts up to 100% polymorph Form 2, or any amount in between - for example, the composition may comprise less than 0.1%, 0.5%, 1%, 2%, 5%. 10%, 20%, 30%, 40% or 50% by weight of polymorph Form 2 based on the total amount of [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyra2olo[l,5-a]pyrimidin-7-yl]-[(S)-I- (3-methyl-[l,214]oxadiazol-5-yl)-propyl]-amine in the composition. Alternatively, the composition may comprise at least 50%, 60%, 70%, 80%, 90%, 95%, 91%, 98%, 99%, 99,5% or 99.9% by weight of polymorph Form 2 based on the total amount of [3-(4- methyl-[l,2,4]oxadiazol-5-y!)-propyl]-amine in the composition. The compounds of the present invention may generally be utilized as the free base. Alternatively, the compounds of this invention may be used in the form of acid addition salts Acid addition sails of the free base amino compounds of the present invention may be prepared by methods well known in the art, and may be formed from organic and inorganic acids. Suitable, organic acids include maJeic, fumaric, benzoic, ascorbic, succinic, methanesulfonic, acetic, oxalic, propionk, tartaric, salicylic, citric, gluconic, lactic, mandelic, cinnamic, aspartic, stearic, palmitic, glycolic, glutamic, and benzenesulfonic acids. Suitable inorganic acids include hydrochloric, hydrobromic, sulfuric, phosphoric, and nitnc acids. Thus, the term "pharmaceutically acceptable salt" of structure ([) is intended to encompass any and all acceptable salt forms. In general, the compounds of structure (I) may be made according to the organic synthesis techniques known to those skilled in ihis field, as well as by the representative methods set forth in the Examples, For example, the synthesis of structure (1) may generally proceed according to the following Reaction Scheme 1 through Reaction Scheme 6, which schemes are presented for purposes of exemplification and not limitation Reacti onSchemeJ Reaction of 7-chloro-pyrazolo-(l,5a]-pyrimidine a with ami no acid ester under anhydrous conditions affords amino acid ester b. Reaction of Cmpd b with NaH and substiluted amjdoxime under anhydrous conditions affords the 5-yl-[l,2,4]oxadiazole Cmpd c. Reaction Scheme 2 Reaction of T-chloro-pyi^zolo-ftal-pyrimidine a with amino acid ester under anhydrous conditions affords amino acid ester b. Compound b is de-esterified in the presence of LiOH to afford amino acid b'. Reaction of Cmpd b1 with amidoxime in the presence of DIG and HOBT affords Cmpd b" which undergoes ring closure upon incubation in pyndine at elevated temperature to afford the 5-yl-[l,2,4]oxadiazole Cmpd . Reaction Scheme 3 Reaction of 7-chloro-pyrazolo-[i,5a]-pyrimidine a with amino acid affords amino acid b'. Reaction of Cmpd b' with arrudoxime in the presence of DIC and HOST affords Cmpd b" which undegoes ring closure upon incubation in pyridine at elevated temperature to afford the 5-yl-(l,2,4]oxadiazole Cmpd c. Reaction Scheme 4 Reaction of 7-chloro-pyra2olo-fl,5a]-pyrimidine a with substituted amine affords Cmpd d, which reacts with brorno ester to afford amino acid ester b. Compound b reacts with amidoxime in the presence of NaH to afford the 5-yl-[l,2,4]oxadia2ole Cmpd (Figure Removed) Reaction of 7-chloro-pyrazolo-(l,5a]-pyrimidine a with aminol and triethylamine (TEA) in aCetonilrile affords aminol e which can be mesylated by ptoluenesulfonyl chlonde in the presence of TEA to afford Cmpd f. Cyano functionaJity can be introduced into Cmpd f affording Cmpd g, which can react with hydroxylamme to give Cmpd h. Compound h undergoes ring closure in the presence of DMA-DMA to afford the the 3-yl-[l,2,4)oxadiazoIeCmpd i. Reaction Scheme 6 Reaction of 7-chloro-p)Tazo1o-[l,5aJ-pyrimidine amino acid ester b with hydrazine giving Cmpd j followed by reaction with eihyl formate giving Cmpd k and ring closure with TsCI and DBU affords the S-y!-[l,3,4]oxadiazole Cmpd 1. Reaction Scheme 7 Reaction of 3-bromo-7-ai7iino-pyrazolo-[l,5a]-pyrimidine amino acid ester m with arylboronic acid under conditions of the Suzuki reaction affords the 3-aryl-7- arruno-pyrazolo-[l,5a]-pyrimidme ammo acid ester b which reacts with NaH and substituted amidoxime to afford Cmpd c. The effectiveness of a compound as a CRF receptor antagonist may be determined by various assay methods. CRF antagonists of this invention may be capable of inhibiting the specific binding of CRF 10 its receptor and ant-agonizing activities associated with CRF. A compound of structure (I) may be assessed for activjiy as a CRF antagonist by one or more generally accepted assays for this purpose, including (but not limited to) the assays disclosed by DcSouza et al. (J. Neuroscience 7:88, 1987) and Battaglia et al (Synapse 1:512, 1987), As mentioned above, CRF antagonists of this invention include compounds which demonstrate CRF receptor affinity. CRF receptor affinity may be determined by binding studies that measure the a b i l i ty of a compound to inhibit the binding of a radiolabeled CRF (e.g., [l25I}tyrosirte-CFR) to its receptor (e.g., receptors prepared from rat cerebral cortex membranes). The radioligand binding assay described by DeSouza et ah (supra, 1987) provides an assay for determining a compound's affinity for the CRF receptor. Such activity is typically calculated from the ICso as the concentration of a compound necessary to displace 50% of the radiolabeled ligand from the receptor, and is reported as a "Kf value calculated by the following equation: where L - radioligand and KD = affinity of radioligand for receptor (Cheng and Prusoff. Biochem. Ptiamacol. 22:3099, 1973). In addition to inhibiting CRF receptor binding, a compound's CRF receptor antagonist activity may be established by the ability of the compound to antagonize an activity associated with CRF. For example, CRF is known to stimulate various biochemical processes, including adenylate cyclase activity. Therefore, compounds may be evaluated as CRF antagonists by their ability to antagonize CRF-stimulated adenylate cycla&e activity by, for example, measuring cAMP levels. The CRF-stimulated adenylate cyclase activity assay described by Battaglia etal. (supra, 1987) provides an assay for determining a compound's ability to antagonize CRF activity. Accordingly, CRF receptor antagonist activity may be determined by assay techniques which generally include an initial binding assay (such as disclosed by DeSouza (supra, 1987)) followed by a cAMP screening protocol (such as disclosed by Battaglia (supra, 1987)). With reference to CRF receptor binding affinities, CRF receptor antagonists of this invention may have a K, of less than 10 pM. In one embodiment of this invention, a CRF receptor antagonist has a EQ of less than luM, and in a another embodiment the K, is less than 0.25 pM (i.e., 250 nM). As set forth in greater detail below, the Kj values may be assayed by the methods set forth in Example 25. CRF receptor antagonists of the present invention having a K; of less than 0.10 ^M (i.e., 100 nM) include Examples 11-1, 11-2, 11-3, 11-4, 11-5, 11-6. 11-9, 11-10, 11-11, 11-13, 11- 17, 11-18, 11-20, 11-23, 11-26, 12-1, 12-2, 12-3, 12-4, 12-5, 12-9. 12-10, 12-11, 13-1, 13- 2, 13-3, 13-4, 13-5, 13-6, 13-7, 13-8, 13-9, 14-1, 14-2, 14-3, 14-4, 15-1, 17-1, 17-2, 17-3, 18-1, 18-2, 19-1, 20-1, 20-2, 21-1, 22-1, 23-2, 24-1, 24-2, 24-4, and 24-6. CRF receptor antagonists of ihe present invention may demonstrate activity at the CRF receptor site, and may be used as therapeutic agents for the treatment of a wide range of disorders or illnesses including endocrine, psychiatric, and "neurological disorders or illnesses. More specifically, CRF receptor antagonists of the present invention may be useful in treating physiological conditions or disorders arising from the hypersecretion of CRF. Because CRF is believed to be an important neurotransmitter that activates and coordinates the endocrine, behavioral and automatic responses to stress, CRF receptor antagonists of the present invention may be useful in the treatment of neuropsychiatric disorders. Neuropsychiatric disorders which may be treatable by the CRF receptor antagonists of this invention include affective disorders such as depression; anxiety-related disorders such as generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, abnormal aggression, cardiovascular abnormalities such as unstable angina and reactive hypertension; and feeding disorders such as anorexia nervosa, bulimia, and irritable bowel syndrome. CRF antagonists may also be useful in treating stress-induced immune suppression associated with various diseases states, as well as stroke. Other uses of the CRF antagonists of this invention include treatment of inflammatory conditions (such as rheumatoid arthritis, uveitis. asthma, inflammatory bowel disease and G.I. motility), pain, Cushing's disease, infantile spasms, epilepsy and other seizures in both infants and adults, and various substance abuse and withdrawal (including alcoholism). Wiihin the context of the present invention, the following terms describing the indications used herein are classified in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, published by the American Psychiatric Association (DSMIV) and/or the International Classification of Diseases, 10th Edition (ICD-lO). The various subtypes of the disorders mentioned herein are contemplated as part of the present invention. Numbers in brackets after the listed diseases below refer to the classification code in DSM-IV. Within the context of the present invention, the term "psychotic disorder" includes :- Schizophrenia including the subtypes Paranoid Type (295.30), Disorganised Type (295.10), Catatonic Type (295.20), Undifferentiated Type (295.90) and Residual Type (295.60); Scbizophreniform Disorder (295.40); Schizoaffective Disorder (295.70) including the subtypes Bipolar Type and Depressive Type; Delusional Disorder (297.1) including the subtypes Erotomanic Type, Grandiose Type, Jealous Type, Persecutory Type, Somatic Type, Mixed Type and Unspecified Type; Brief Psychotic Disorder (298.8); Shared Psychotic Disorder (297.3); Psychotic Disorder Due 10 a General Medical Condition including the subtypes With Delusions and With Hallucinations; Substance-Induced Psychotic Disorder including the subtypes With Delusions (293.81) and With Hallucinations (293.82); and Psychotic Disorder Not Otherwise Specified (298.9). The compounds of the present invention including salts and pharmaceutical!y acceptable solvates thereof may also be of use in the treatment of the following disorders:- Depression and mood disorders including Major Depressive Episode, Manic Episode, Mixed Episode and Hypomanic Episode; Depressive Disorders including Major Depressive Disorder, Dysthymic Disorder (300.4), Depressive Disorder Not Otherwise Specified (311); Bipolar Disorders including Bipolar I Disorder, Bipolar II Disorder (Recurrent Major Depressive Episodes with Hypomanic Episodes) (296.89), Cyclothymic Disorder (301.13) and Bipolar Disorder Not Otherwise Specified (296.80); Other Mood Disorders including Mood Disorder Due to a General Medical Condition (293.83) which includes the subtypes With Depressive Features, With Major Depress!velike Episode, With Manic Features and With Mixed Features), Substance-Induced Mood Disorder (including the subtypes Wilh Depressive Features, With Manic Features and With Mixed Features) and Mood Disorder Not Otherwise Specified (296.90): Anxiety disorders including Social Anxiety Disorder, Panic Attack, Agoraphobia, Panic Disorder, Agoraphobia Without History of Panic Disorder (300.22), Specific Phobia (300.29) including the subtypes Animal Type, Natural Environment Type, Blood-Injection-Injury Type, Situational Type and Other Type), Social Phobia (300.23), Obsessive-Compulsive Disorder (300.3), Posttraumatic Stress Disorder (309.81), Acute Stress Disorder (308.3), Generalized Anxiety Disorder (300.02), Anxiety Disorder Due to a General Medical Condition (293.84), Substance-Induced Anxiety Disorder and Anxiety Disorder Not Otherwise Specified (300.00): Substance-related disorders including Substance Use Disorders such as Substance Dependence, Substance Craving and Substance Abuse; Substance-Induced Disorders such as Substance Intoxication, Substance Withdrawal, Substance-Induced Delirium, Substance-Induced Persisting Dementia, Substance-Induced Persish'ng Amnestic Disorder. Substance-Induced Psychotic Disorder, Substance-Induced Mood Disorder, Substance-Induced Anxiety Disorder, Substance-Induced Sexual Dysfunction, Substance-Induced Sleep Disorder and Hallucinogen Persisting Perception Disorder (Flashbacks); Alcohol-Related Disorders such as Alcohol Dependence (303.90), Alcohol Abuse (305.00), Alcohol Intoxication (303.00), Alcohol Withdrawal (291.81), Alcohol Intoxication Delirium, Alcohol Withdrawal Delirium, Alcohol-Induced Persisting Dementia, Alcohol-Induced Persisting Amnestic Disorder, Alcohol-Induced Psychotic Disorder, Alcohol-Induced Mood Disorder, Alcohol-Induced Anxiety Disorder, Alcohol- Induced Sexual Dysfunction, Alcohol-Induced Sleep Disorder and Alcohol-Related Disorder Not Otherwise Specified (291.9); Amphetamine (or Amphetajr>ine-Like)-Related Disorders such as Amphetamine Dependence (304.40), Amphetamine Abuse (305.70), Amphetamine Intoxication (292.89), Amphetamine Withdrawal (292.0), Amphetamine Intoxication Delirium, Amphetamine Induced Psychotic Disorder, Amphetamine-Induced Mood Disorder, Amphetamine-Induced Anxiety Disorder, Amphetamine-Induced Sexual Dysfunction, Amphetamine-Induced Sleep Disorder and Amphetamine-Related Disorder Not Otherwise Specified (292.9); Caffeine Related Disorders such as Caffeine Intoxication (305.90), Caffeine-Induced Anxiety Disorder, Caffeine-Induced Sleep Disorder and Caffeine-Related Disorder Not Otherwise Specified (292.9); Cannabis-Related Disorders such as Cannabis Dependence (304.30), Cannabis Abuse (305.20), Cannabis Intoxication (292.89), Cannabis Intoxication Delirium, Cannabis-Induccd Psychotic Disorder, Cannabis-Induced Anxiety Disorder and Cannabis-Relaied Disorder Not Otherwise Specified (292.9); Cocaine-Related Disorders such as Cocaine Dependence (304.20), Cocaine Abuse (305.60). Cocaine Intoxication (292.89), Cocaine Withdrawal (292.0), Cocaine Intoxication Delinum, Cocaine-Induced Psychotic Disorder, Cocaine-Induced Mood Disorder, Cocaine-Induced Anxiety Disorder, Cocaine-Induced Sexual Dysfunciion, Cocaine-Induced Sleep Disorder and Cocaine-Related Disorder Not Otherwise Specified (292,9); Hallucinogen-Related Disorders such as Hallucinogen Dependence (304.50), Hallucinogen Abuse (305.30), Hallucinogen Intoxication (292.89), Hallucinogen Persisting Perception Disorder (Flashbacks) (292.89), Hallucinogen Intoxication Delirium, Hallucinogen-Induced Psychotic Disorder, Hallucinogen-Induced Mood Disorder, Hallucinogen-Induced Anxiety Disorder and Hallucinogen-Related Disorder Not Otherwise Specified (292.9); Inhalant-Related Disorders such as Inhalant Dependence (304.60), Inhalant Abuse (305.90), Inhalant Intoxication (292.89), Inhalant Intoxication Delirium, Inhalant-Induced Persisting Dementia, Inhalant-Induced Psychotic Disorder, Inhalant-Induced Mood Disorder, Inhalant-Induced Anxiety Disorder and Inhalant-Related Disorder Not Otherwise Specified (292.9); Nicotine-Related Disorders such as Nicotine Dependence (305.1), Nicotine Withdrawal (292.0) and Nicotine-Related Disorder Not Otherwise Specified (292.9); Opioid-Related Disorders such as Opioid Dependence (304.00), Opioid Abuse (305.50), Opioid Intoxication (292.89), Opioid Withdrawal (292.0), Opioid Intoxication Delirium, Opioid-Induced Psychotic Disorder, Opioid-Induced Mood Disorder, Opioid-Induced Sexual Dysfunction, Opioid-Induced Sleep Disorder and Opjoid-Related Disorder Not Otherwise Specified (292.9); Phencychdine (or Phencyclidine-Like)-Related Disorders such as Phencyclidine Dependence (304.60), Phencyclidine Abuse (305.90), Phencyclidine Intoxication (292.89), Phencyclidine Intoxication Delirium, Phencyclidine-Induced Psychotic Disorder, Phencyclidine-lnduced M6od Disorder, Phencyclidine-Induced Anxiety Disorder and Phencyclidine-Related Disorder Not Otherwise Specified (292.9); Sedative-, Hypnotic-, or Anxiolytic-Related Disorders such as Sedative, Hypnotic, or Anxiolytic Dependence (304.10), Sedanve, Hypnotic, or Anxiolytic Abuse (305.40), Sedative, Hypnotic, or Anxiolytic Intoxication (292.89), Sedative. Hypnotic, or Anxiolytic Withdrawal (292 0), Sedative, Hypnotic, or Anxiolytic Intoxication Delirium, Sedative, Hypnotic, or Anxiolytic Withdrawal Delirium, Sedative-, Hypnotic-, or Anxiolytic-Persisting Dementia, Sedative-, Hypnotic-, or Anxiolytic- Persisting Amnestic Disorder, Sedative-, Hypnotic-, or Anxiolytic-Induced Psychotic Disorder, Sedative-, Hypnotic-, or Anxiolytic- Induced Mood Disorder, Sedative-, Hypnotic-, or Anxiolytic-Induced Anxiety Disorder Sedative-, Hypnotic-, or Anxiolytic-Induced Sexual Dysfunction, Sedative-, Hypnotic-, or Anxiolyiic-Induced Sleep Disorder and Sedative-, Hypnotic-, or Anxiolytic-Reiated Disorder Not Otherwise Specified (292.9); Polysubstance-Related Disorder such as Polysubsiance Dependence (304.80); and Other (or Unknown) Substance-Re)aied Disoiders such as Anabolic Steroids. Nitrate Inhalants and Nitrous Oxide: Sleep disorders including primary sleep disorders such as Dyssomnias such as Primary Insomnia (307.42), Primary Hypersomnia (307.44), Narcolepsy (347), Breathing-Related Sleep Disorders (780.59), Circadian Rhythm Sleep Disorder (307.45) and Dyssomnia Not Otherwise Specified (307.47); primary sleep disorders such as Parasomnias such as Nightmare Disorder (307.47), Sleep Terror Disorder (307.46), Sleepwalking Disorder (307.46) and Parasomnia Not Otherwise Specified (307.47); Sleep Disorders Related to Another Menial Disorder such as Insomnia Related to Another Mental Disorder (307.42) and Hypersomnia Related to Another Mental Disorder (307.44); Sleep Disorder Due to a General Medical Condition; and Substance-Induced Sleep Disorder including the subtypes Insomnia Type, Hypersomnia Type, Parasomnia Type and Mixed Type: Eating disorders such as Anorexia Nervosa (307-1) including the subtypes Restricting Type and Binge-Eating/Purging Type; Bulimia Nervosa (307.51) including the subtypes Purging Type and Nonpurging Type; Obesity; Compulsive Eating Disorder; and Eating Disorder Not Otherwise Specified (307.50): Autistic Disorder (299.00); Attention-Deficit /Hyperactivity Disorder including the subiypes Attention-Deficit /Hyperactivity Disorder Combined Type (31401), Attention-Deficit /Hyperactivity Disorder Predominantly Inattentive Type (314.00), Atiention-Deficit /Hyperactivity Disorder Hyperactive-Impulse Type (314.01) and Attention-Deficit /Hyperaciivity Disorder Not Otherwise Specified (314.9); Hyperkinetic Disorder; Disruptive Behaviour Disorders such as Conduct Disorder including the subtypes childhood-onset type (321.81), Adolescent-Onset Type (312.82) and Unspecified Onset (312.89), Oppositional Defiant Disorder (313.81) and Disruptive Behaviour Disorder Not Otherwise Specified; and Tic Disorders such as Tourette's Disorder (307.23): Personality Disorders including the subtypes Paranoid Personality Disorder (301.0), Schizoid Personality Disorder (301.20), Schizotypal Personality Disorder (301,22), Antisocial Personality Disorder (301.7), Borderline Personality Disorder (301,83), Histrionic Personality Disorder (301.50), Narcissistic Personality Disorder (301,81). Avoidam Personality Disorder (301.82), Dependent Personality Disorder (301.6), Obsessive-Compulsive Personality Disorder (301.4) and Personality Disorder Not Otherwise Specified (301.9): Enhancement of cognition including the treatment of cognition impairment in other diseases such as schizophrenia, bipolar disorder, depression, other psychiatric disorders and psychotic conditions associated with cognitive impairment, e.g. Alzheimer's disease: and Sexual dysfunctions including Sexual Desire Disorders such as Hypoactive Sexual Desire Disorder (302.71), and Sexual Aversion Disorder (302.79); sexual arousal disorders such as Female Sexual Arousal Disorder (302.72) and Male Erectile Disorder (302.72); orgasmic disorders such as Female Orgasmic Disorder (302.73), Male Orgasmic Disorder (302.74) and Premature Ejaculation (302.75); sexual pain disorder such as Dyspareunia (302.76) and Vaginismus (306.51); Sexual Dysfunction Not Otherwise Specified (302.70); paraphilias such as Exhibitionism (302.4), Feiishism (302.81), Frocteurism (302.89), Pedophilia (302.2), Sexual Masochism (302.83). Sexual Sadism (302.84), Transvestic Fetishism (302.3), Voyeurism (302,82) and Paraphilia Noi Otherwise Specified (302.9); gender identity disorders such as Gender Identity Disorder in Children (302.6) and Gender Identity Disorder in Adolescents or Adults (302.85); and Sexual Disorder Not Otherwise Specified (302.9). All of the various forms and sub-forms of the disorders mentioned herein are contemplated as part of the present invention. "Treatment" includes prophylaxis, where this is appropriate for the relevant condilion(s). Jn another embodiment of the invention, pharmaceutical compositions containing one or more CRF receptor antagonists are disclosed. For the purposes of administration, the compounds of the present invention may be formulated as pharmaceutical compositions. Pharmaceutical compositions of the present invention include a pharmaceutically effective amount of a CRF receptor antagonist of the present invention (i.e.. a compound of structure (I)) and a pharmaceutically acceptable carrier or diluent. Thus, the CRF receptor antagonist is present in the composition in an amount which is effective to treat a particular disorder. In one embodiment of the invention, the pharmaceutical compositions of the present invention may include a CRF receptor antagonist in an amount from 0.1 mg to 250 mg per dosage depending upon the route of administration. In another embodiment the dosage may be from 1 mg to 60 mg. In other embodiments, the dosage may be, for example, 5 mg, 10 mg, 15 mg or 20 mg. Appropriate concentrations and dosages can be readily determined by one skilled in the art. Pharmaceuiically acceptable carrier and/or diluents are familiar to those skilled in the art. For compositions formulated as liquid solutions, acceptable carriers and/or diluents include saline and sterile water, and may optionally include antioxidants, buffers, bacterioslats and other common additives. The compositions can also be formulated as pills, capsules, granules, or tablets which contain, in addition to a CRF receptor antagonist, diluenls, dispersing and surface active agenls, binders, and lubricants. One skilled in this art may funher formulate the CRF receptor antagonist in an appropriate manner, and in accordance with accepted practices, such as those disclosed in Remington's Phannaceutica! Sciences, Gennaro, Ed., Mack Publishing Co., Easton, PA 1990. In addition, prodrugs are also included within the context of this invention. Prodaigs are any covalently bonded carriers that release a compound of structure (I) in vivo when such prodrug is administered to a patient. Prodrugs are generally prepared by modifying functional groups in a way such that the modification is cleaved, either by routine manipulation or in. vivo, yielding the parent compound. With regard to stereoisomers, the compounds of structure (I) may have chiral centers and may occur as racemates, racemic mixtures and as individual enantiomers or diastereomers. All such isomeric forms are included within the present invention, including mixtures thereof. Furthermore, some of the crystalline forms of the compounds of structure (I) may exist as polymorphs, which are included in the present invention. In addition, some of the compounds of structure (1) may also form solvates with water or other organic solvents. Such solvates are similarly included within the scope of this invention. In another embodiment, the present invention provides a method for treating a variety of disorders or illnesses, including endocrine, psychiatric and neurological disorders or illnesses. Such methods include administering of a compound of the present invention to a mammal (e.g., a person) in an amount sufficient to treat the disorder or illness. Such methods include systemic administration of a pharmaceutical composition containing a pharmaceutically effective amount of a CRF receptor antagonist of this invention. As used herein, systemic administration includes oral and parenteral methods of administration. For oral administration, suitable pharmaceutical compositions of CRF receptor antagonists include powders, granules, pills, tablets, and capsules as well as liquids, syrups, suspensions, and emulsions. These compositions may also include flavorants, preservatives, suspending, thickening and emulsifying agents, and other pharmaceutically acceptable additives. For parental administration, the compounds of the present invention can be prepared in aqueous injection solutions which may contain, in addition to the CRF receptor antagonist, buffers, antioxidants, bacteriostats, and other additives commonly employed in such solutions. ]n another embodiment, the present invention permits the diagnostic visuaJization of specific sites within the body by the use of radioactive or non-radioactive pharmaceutical agents Use of a compound of the present invention may provide a physiological, functional, or biological assessment of a patient or provide disease or pathology detection and assessment. Radioactive Pharmaceuticals are employed in scintigraphy. positron emission tomography (PET), computerized tomography (CT), and single photon emission computerized tomography (SPECT). For such applications, radioisotopes are incorporated of such elements as iodine (I) including U3I (PET), I25I (SPECT), and m], technetium (Tc) including 9*Tc (PET), phosphorus (P) including 3IP and 32P, chromium (Cr) including 5lCr, carbon (C) including 1!C, fluorine (F) including 18F, thallium (Tl) including M1TI, and like emitters of positron and ionizing radiation. Non-radioactive pharmaceuticals are employed in magnetic resonance imaging (MRI), fluoroscopy, and ultrasound. For such applications, isotopes are incorporated of such elements as gadolinium (Gd) including 15IGd, iron (Fe), barium (Ba), manganese (Mn). and thallium (Tl). Such entities are also useful for identifying the presence of particular target sites in a mixture and for labeling molecules in a mixture. The following examples are provided for purposes of illustration and not for purposes of limitation. EXAMPLES The CRF receptor antagonists of this invention may be prepared by the methods disclosed in the Examples, Example 25 presents a method for determining the receptor binding affinity, and Example 26 discloses an assay for screening compounds of this invention tor CRF-siimulated adenylate cyclase activity. Abbreviations; AcCN, MeCN: acetonitrile AcCN: Acetonitrile DBU Diaminobutyric acid DCM: Dichloromethane DEAD: diethylazodicarboxylate DIG: N.N'-Diisopropylcarbodiimide DEU: N.N'-diisopropylurca DMA-DMA: N,N-dimethylacetamide dimethyl acetal DME: 1,2-dimethoxyethane OITF: Dimethylformamide DMF-DMA: N^N-dimethylformamide dimethyl acelal EAA: Ethyl acctoacetate HOST: 1-Hydroxybenzotriazole LC/MS: liquid chromatography-mass speccroscopy MDA: Malondialdehyde bis-di methyl acetal MsCl: Methanesulfonyl chloride NaBH(OAc)3: Sodium Triacetoxyborohydride Pd-C: Palladium (10 %) on Carbon TEA; Triethylamme TFA: Trifluoroacetic acid THF: Tetrahydrofuran TosMIC: Tosylmethyl isocyanide TsCl; p-tolunesulfonyl chloride TsOH: p-Toluenesulfonic acid Prep. HPLC-MS Gilson HPLC-MS equipped with Gilson 215 auto-sarnpler/fraction collector, an UV detector and a ThermoFinnigan AQA Single QUAD Mass detector (electrospray); HPLC column: BHK ODS-O/B, 5 u, 30x75 mm HPLC gradients: 35 mL/min, 10 % acetonitrile in water to 100 % acetonitrile in 1 min, maintaining 100 % acetonitrile for 3 min. Analytical Method I --High Performance Liquid Chromatogfaphy (HPLC-MS) Platform: HP 1100 senes: equipped with an auto-sampler, an UV detector (220 nM and 254 nM), a MS detector (electrospray); Column: Phenomenex SynergiMAX-RP, 4 micron, 2x 50 mm; Mobile phase: A=water, 0.025 % TFA; B=acetonitrile, 0.025% TFA; Flow rate: 1.0 mL/min; Gradient: 5% B/95% A to 95% B/5% A over 13 min, then hold 2.5 min; Analytical Meihod 2 -- Supercritical Fluid Chromatographv (SFQ Platform: Burger FCM1200 SFC pump, Agilent Diode Array Detector. Agilent Model 220 MicropliUe autosampler, Agilent Model 1946 MSB (APCI interface); Column: Berger Pyridine 60A, 4 micron, 3x 150 mm; Solvents: SFC Grade COj, Optima-grade methanol with 1.5% water and 0.025% ethanesulforiic acid; Flow rate: 4.0 mJL/min. 120 Bar backpressure; Gradient: 5-55% methanol/CO2 in 2.4 min. Analytical Method 3 - Ajnjlyiipal HPLC-MS (LC-MS) Platform: HP 1100 series equipped with an auto-sampler, a UV detector (220 nM and 254 nM), and an MS detector (APCI); Column: Waters XTerra 3 x 250 rnm; Solvent A: water with 0.025 % TFA Solvent B: acetonitrile with 0.025% TFA Flowrate: 1,0 mL/min; Gradient: 5% B for 1.55 min, [hen 10 to 90 % B over 46 min (47.55 min total) Method.4 - Analvocai HPLC-MS CLC-MS, Platform: HP/Agilent 1100 series: equipped with an auto-sampler, a UV detector (220 nM and 254 nM).. ind an MS detector (APCI): Column; Phenomonex SynergymaK RP 2.0 x 50 mm; Flownate: LOmL/min; Solvent A: 0.05% TFA in water Solveni B: 0.05% TFA in acetonitrile Gradient: 5 % B for 0,25 min, then from 5% B to 90 % B from 0.25 to 2.25 then 90% B from 2.25 to 3.25 min. EXAMPLE,! SYNTHESIS OF REAGENT [5-(7-CHLORO-2,5-DrviETHYL-PYRA20LOf l,5-AjPYJUMTDix-3-vt.)- 4 -METHYL-PYKIDIN-2- YL] -DMETHYL-AMINE Step I A: To a mixture of 2-amino-4-pico!ine (33 g), NaBHjCN (57 g), formaldehyde (37% aq. solution, 240 mL) in acetomirile (1 L) and water (200 mL) was added drop-wise acetic acid (60 mL) at 0 °C in 2 hr. The resultant solution was stirred at RT for 7 days and then concentrated in vacua. The residue was basified with solid NaOH to pH 10 and extracted with hexanes (3x 700 mL). The combined extract was washed with IN aq. NaOH and brine, dried over Na?SO4 and evaporated in vacua to give 2-dimethylamino-4- methylpyridine as a colorle$s oil (Cmpd la, 36 g, 88%). 'H NMR (CDClj): 2.26 (s, 3H), 3.07 (s, 6H), 6.33 (s, 1H), 6.40 (d, 1H). 8.02 (d, 1H); MS (CI) m/e 137 (MH*). Step IB: A mixture of Cmpd la (32 g), NaiC05 (30 g) in DCM (50 mL) and water (400 mL) was treated dropwise with a solution of bromine (13 mL) in DCM (50 mL) at 0 °C in 0.5 hr. The resultant light brown suspension was stirred at 0 °C for 0.5 hr. The resultant was extracted with hexanes (2x 600 mL,) and the combined extract was washed with brine, dried over NajSC and evaporation in vacua. The crude resultant was purified by chromatography on silica gel with 1:5 ethyl acetate/hexanes to give 5-bromo-2- dimethylamino-4-methylpyridine as a tan solid (Cmpd Ib, 78% yield). 'H NMR (CDCb): 2.30 (s, 3H), 3.04 (s, 6H), 6.38 (s, 1H), 8.14 (s, 1H); MS (CI) m/e 216 (MTf). Into a suspension of magnesium (11.3 g) in THF (20 mL) was added a quarter portion of a solution of Cmpd Ib (48.5 g) from Step IB in THF (100 mL). The reaction was initiated with 5 drops of 1,2-dibromoethane with slightly heating. After initiation of the reaction 10 mL of THF was added. The rest of the solution of Crnpd Ib was added dropwise to maintain a gentle reflux. After completion of addition the mixture was stirred at RT for 0.5 hr before DMF (1.5 eq.) was slowly injected at 0 °C. The resultant mixture was stirred at RT overnight and quenched with saturated aq. NRjCI. The resultant was extracted with ether (2 x 500 mL) and the combined extract was washed with brine, dried over 3vlgSO4, filtered and concentrated in vacua. The resultant was purified by chromatography on silica gel with 1:5 ethyl acetate/hexanes to afford 2-dimethylarnino- 4-methy]-5-formylpyridine as a tan solid (Cmpd lc, 77% yield). The analytic sample was obtained by crystallization from eiher/hexanes. 'H NMR (CDC13): 2.57 (s, 3H). 3.11 (s, 6H),6.28(s, lH),8.43(s, )H),9.87(s, 1H); MS (Cl)m/e 165 (MPT). Step ID: Into a suspension of tBuOK (J 2.5 g) in DME (70 mL) at -50 °C was added dropwise a solution of TosMIC (15.6 g) in DME (70 mL). The brown solution was stirred at -50 °C for ]0 mm before a solution of Cmpd It (11 g) in DME (70 mL) was added dropwise. The resultant mixture was stirred at -50 "C for 0.5 hr and quenched with methanol (70 mL). This mixture was heated to reflux for 1 hr and the solvent was evaporated and partitioned in ethyl acetate-water. The organic layer was washed with bnne, dried over MgSO4 and filtered through a silica gel pad with ethyl acetate. This work-up gave 2-dimethylarn.ino-4-rnethyl-5-(cyanomethyl)pyridine as a yellow solid (Cmpd Id, 9.5 g, 80%) 'H NMR (CDClj): 2.3l(s, 3H), 3.08 (s, 6H), 3.54 (s, 2H), 6.36 (s, LH), 7.99 (s, 1 H); MS (CI) m/e 176 (MH*) Step IE: Into a suspension of Cmpd Id (40 g, 0.23 mol) and NaH (2.5 eq.) in THF (100 mL) was added about 5 mL of ethyl acetate. The mixture was stirred at RT until an exothermic reaction started and hydrogen evolved vigorously. Ethyl acetate (50 mL) was then added dropwise to maintain a gentle reflux. The mixture was stirred at RT for 2 hr before it was quenched with water (100 mL). The organic phase was separated and the aqueous phase was washed several times with ethyl ether. The aqueous phase was then acidified with acetic acid, and the resultant was extracted with ethyl acetate (5 x 800 mL). The combined extract was washed with brine (50 mL) and dried over MgSCU. Concentration in vacua gave the keto form l-cyano-l-(6-dimethylamino-4-methylpyridin- 3-yl)acetone and the 3-hydroxy-but-2-enenitrile enol form (Cmpd le) as a brown solid (40 g, 80% yield). 'H NMR (CDC13): 1:1 rruxtute of enol and ketone form, 2.24 (s, 1.5x3H), 2.32 (s. 0 5x3H), 2.88 (s, 0.5x6H), 3.09 (s, 0.5x6H), 4.50 (brs, O.SxlH), 4.62 (s, O.SxlH), 6.13 (s, 0 SxlH), 6.35 (s, O.SxlH), 7.60 (s, O.SxlH), 8.05 (s, 0.5xlH); MS (Ct) m/e 218 (MH*). StepJJF; A mixture of Cmpd le (30 g) and hydraiine hydrobromide (62 g) in ethanol (150 mL) and water (20 mL) was heated to reflux for 1 hr. Ethanol was removed in vacua and the residue was diluted with water (50 mL). The aqueous phase was basified with solid NaiCOj and the resultant was extracted with ethyl acetate. The extract was dned over MgSO4, filtered and concentrated in vacuo to give 3-amino-4-(6-dimethylamino-4- methylpyndin-3 yl)-5-methylpyrazole as a brownish oil (Cmpd If, 30g, 93% yield,) which was crystallized from ether-hexanes. 'H NMR (CDCb): 2.07 (s, 3H), 2.14 (s, 3H), 3.10 (s, 6H), 4.10 (brs. 3H), 6.45 (s, IH), 7.92 (s, IH); MS (CI) m/e 232 (MH*) Step IG: A solution of Cmpd If (29.5 g) and ethyl acetoacetate (2.5 eq.) in dioxane (100 mL) was heated to reflux for 20 hr. The suspension was cooled, and elher (200 mL) was added. The solid was collected by vacuum filtration and 2,5-dimethyl-3-(6- dimethylamJno-4-methylpvridin-3-yl)-7-hydroxvpyrazolo[l,5-a]pyrimidine was obtained as a tan solid (Cmpd Ig, 23.5 g, 62% yield). The filtrate was concentrated in vacuo and the residue was dissolved in water (50 mL). This aqueous phase was extracted with ether (3x 300mL) to remove starting material and impurity. The product was then extracted with DCM (5x 300 mL) affording another 6 g (total yield 78%) of Cmpd Ig. 'H NMR (CDCb): 2.10 (s, 3H), 2.20 (s. 3H), 2,33 (s, 3H), 2.91 (s. 6H), 5.64 (s, IH), 6.24 (s, IH), 7.65 (s, IH). MS (CI) rn/e 298 (MM*) A suspension of Cmpd Ig (11 g) and POClj (2 eq.) in acetonitrile (50 mL) was heated to reflux for 8 hr. The reaction was quenched with ice and basified with Na2CO3. The product was extracted with ethyl acetate (2x 200 mL). The extract was dried over MgSCXj, filtrated through a silica gel pad and concentrated in vacua to give [5- (7-Chloro-2,5-djmethyl-pyra2olo[l,5-a]pyrimidin-3-yl)-4-methyl-pyridin-2-yl]-dimethylamine as a yellowish solid (Cmpd Ib, 11.5 g, 99% yield). 'H NMR (CDCb): 2.13 (s, 3H), 2.43 (s, 3H), 2.53 (s, 3H), 3.11 (s, 6H), 6.49 (s, IH), 6.78 (s, IH), 8.01 (s, LH); MS (CI) EXAMPLE 2 SYNTHtSIS OF REAGENT (2,4-DlMETHOXY-PHENYL)-ACETONrreiLE Into a suspension t-BuOK (47.3 g) in DME (150 mL) at -30 °C (dry ice/acetone bath) was added dropwise a solution of TosMlC (58.8 g) in DME (J50 mL), keeping the temperature of the mixture below -30 °C. The solution was stirred and allowed to coo! to -60 °C over 10 minutes before a solution of 2,4- dimethoxybenzaidehyde (50 gl) in DME (150 mL) was added dropwise, keeping the temperature of the reaction mixture below -50 °C. The reaction mixture was stirred at -50 to -60 °C for Ihr, then methane! (200 mL) was added. This mixture was heated to reflux for 2hr. The solvent was evaporated and the residue was partitioned between ethyl acetate and water with acetic acid (40 mL) added. The aqueous layer was extracted with one additional portion of ethyl acetate, then the combined ethyl acetate layers were washed with bnne, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography, eluting with 1:1 hexanes/ethyl acetate to provide 2 (48.8 g). EXAMPLE 3 SYNTHESIS OF REAGENTS I-CHLORO^-METHOXY-BENZALDEHYDE AND (2-CHLORO-4- METHOXY-PHENYL)-ACETON1TRILE 2-chIoro-4-hydroxybenzaldehyde (9.56 g) and KiCOj (25.3 g) were stirred with DMF (30 mL) at RT for 30 min. lodomethane (4.0 mL) was added, the reaction vessel was sealed, and the mixture was stirred at RT for 16 hr. 300 mL of 2:1 hexanes/eihyl acetate was added, after which the mixture was washed 3 times with water and once with brine. Thq organic layer was dried over sodium sulfate. filtered then evaporated to a volume of about 50 mL. The precipitate which formed was filtered and washed with hexanes to provide Cmpd 3a as a tan solid (6.0 g). Step3B: Formation of the acetoniirile Cmpd 3b followed the procedure of Step 2 employing t-BuOK and TosMlC in DME. EXAMPLE 4 SYNTHESIS OF REAGENT 7-CHL.ORO-3-(4-METHOXY-2-METHYL-PHENYL)-2,5-DIMETHYLPYRA20LO[ 1,5-A]PYR1MIDINE Sodium hydride (12.0 g of 60% suspension in oil) was added to a solution of 4-mcthoxy-2-methylphenylacetonitrile (30 g) in anhydrous THF (300 mL) at RT under nitrogen. About 2 mL of ethyl acetate was added and the mixture was heated gradually to an internal temperature of 66 C. After about 10 minutes a vigorous reaction ensued, and healing was discontinued while additional ethyl acetate (75 mL) was added dropwise over about 20 minutes to maintain reflux. Vigorous hydrogen evolution was observed. By the end of the ethyl acetate addition, ihe reaction mixture began to cool, and the mixture was stirred and allowed to cool over 3 hr. 150 mL water was added followed by 300 mL ether. The aqueous layer was washed with two additional portions of ether. The ether extracts were discarded The aqueous layer was acidified with 20 mL concentrated hydrochloric acid (pH ~5), then the mixture was extracted with three portions of ethyl acetate. The combined ethyl acetate extracts were dried over sodium sulfatc, filtered and evaporated to give crude ketonitrile 4a as a slightly amber oil (39 g) which was carried forward without further purification. Alternate Step4A: Sodium hydride (35.44 g of 60% suspension in oil, 1.48 mot) was added to a solution of 4-methoxy-2-methylphenylacetonitrile (148.8 g, 0.92 mo)) in anhydrous THF (2 L) at it. EtOAc (30 mL) was added and the mixture was heated gradually to an internal temperature of 70.1 °C. Reaction initiated, and heating was discontinued immediately by removing the heating mantle completely. EtOAc (374 mL, total 4.14 mol) was added dropwise to maintain reflux. Vigorous hydrogen evolution was observed and the reaction was stirred for 2 hours after complete EtOAc addition. Water (750 mL) was added, followed by hexane (750 mL) with vigorous stirring and the aqueous layer was separated and acidified with cone. HC1 to pH ~2. The aqueous layer was extracted with EtOAc (3 x 400 mL) and the combined extracts dried (MgSO4) and concentrated in vacua to afford 4a as an amber colored oil (183.8 g, 0.90 mol, 98 %, 99 % purity). Step4B: A mixture of crude 4a (37.8 g) and hydrazine monohydrobromide (23.1 g) was suspended in absolute ethanol (225 mL) and water (25mL). The mixture was refluxed for approximately 3 hr. The reaction mixture was allowed to cool, then the solvent was evaporated. Ethyl acetate was added, and the mixture neutralized by addition of saturated aq. NaHCOj (200 mL), and the mixture was extracted with ethyl acetate (4x 100 mL), The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtered and evaporated to give crude Cmpd 4b as a pale orange oil (45 g) which was carried forward without further purification. Alternate Step 48: Compound 4a (183.8 g, 0.9 mol) was dissolved in EtOH (1.09L) and water (109 mL) and hydrazine hydrobromide (112.39 g, 0.99 mol) was added. The mixture was refluxed (90 "C bath temperature) for 2.5 h, at which time LC/MS monitoring showed complete reaction. The reaction mixture was allowed to cool and concentrated in vacua to remove EtOH and partitioned between NaHCOj (950 mL, sat. aq.) and EtOAc (400 mL). The aqueous layer was separated and extracted further with EtOAc (3 x 400 mL) and the combined organic layers were washed with brine (400 mL), dried (MgSOd) and concentrated in vacua to give the crude aminopyrazole 4b as an amber colored oil (168.8. 80 % pure), which was carried on without further purification. Step 4C: Ethyl acetoacetaie (EAA) (28.4 mL) was added to a solution of 4b (40.2 g, 0.18 mol) in dry dioxane (180 mL). The mixture was refluxed at 115 °C for about 20 h, during which time pyrazolopyrimtdine 4c precipitated from solution as a white solid. The reaction mixture was cooled and the precipitate was filtered and washed with cold ether. The precipitate was then dried in vacua to yield 22.5 g (0.079 mol, 42.7%) of Cmpd 4c as an off-white solid. Alternative Step 4C: Ethyl acetoacetate (EAA) (200 mL) was added to a solution of the crude 4b (180 g, 0 62 mol) in absolute ethanol (500 mL) and glacial acetic acid (500 mL). The mixture was heated to reflux for 2 h, during which time pyrazolopyrimidme 4c precipitated from solution as a while solid. The reaction mixture was cooled and the precipitate was filtered and washed with cold ether. The precipitate was then dried in vacua to yield 131 g (0.46 mol, 75%) of Cmpd 4c as an off-white solid. Siep4D: Phosphorous oxychloride (12 mL) was added to a suspension of 4c (12.1 g) in anhydrous acetonitrile (60 mL) at RT. The mixture was heated at 80 C for 30 h, at which point the reaction mixture was a clear, deep-red solution. The reaction mixture was poured onto 300 mL of ice/water, and the reaction flask was rinsed with 100 mL ethyl acetate. The mixture was then stirred and neutralized with sat. aq. sodium carbonate. The red mixture became yellow upon neutralization. The layers were separated and the aqueous layer was extracted with ethyl acetate (4x 100 mL). The combined organic layers were washed with brine (100 mL). dried over magnesium sulfate, filtered, and concentrated to give a clear brown oil. The crude product was chromatographed on silica gel using 2:1 hexanes/ethyl acetate, giving Cmpd 4d (12.1 g , 94%) as a clear yellow oil, which solidifed upon standing. Alternate Step 4D: To a suspension of pyrazolopyrirnidine 4c (235.1 g, 0.83 mol) in anhydrous acetomtnle (1.2 L) was added phosphorous oxychloride (232 mL, 2.49 mol) at rt. The mixture was heated to 80 °C and stirred for 20 h and allowed to cool and concentrated in vacua to approximately 1/4 the volume. Ice chips and water were carefully added with stirring to make the total volume up to 1 L. Ensuring the temperature was always below 5 °C using an ice bath and adding more ice chips to the mixture, the pH was brought to around 6-7 using NaOH (2 M, aq.). The resulting cold suspension was extracted with EtOAc (3 x 500 mL) and the combined organic layers dried (MgS04) and concentrated in vacua to give chloropyrimidine 4d as a red waxy crystalline solid (258.3 g, 93 % purity), which was used directly for the next step. Also prepared by this method were: 4e 2>5-dimethyl-3-(2,4-dimethoxvphenyl)-7-cnloropyrazolo[lv5-a]- pyrimidine (starting from 2); 4f 2,5-dinieihyl-3-(2-chloro-4-methoxyphenyl)-7-chloropyrazolo(l,5- a]-pynmidine (starting from 3b); and 4g 2,5-dimethyI-3-(4-ethoxyphenyl)-7-chloropyrazolo(l ,5-a]- pyrimidine (starting from 4-elhoxyphenylacetonitrile). EXAMPLE 5 SYNTHESIS OF REAGENT 2-(3-BROMO-2,5-DiMETHYL-pYRAZOLo{ 1,5-A]prwMiDiN-7- YlAMINO)-BUTYRJC ACID METHYL ESTER Step SA: A solution of 3-amino-5-methylpyrazole (20.0 g), ethyl acetoacetate (32.0 g), acetic acid (6 mL), and dioxane (ISO mL) was refluxed for 16hr. A while solid precipitated, which was collected by filtration. The filter cake was washed with ether to provide 5a (29.0 g, 86 %) as a white solid. Step SB: To a suspension of 5a (5.0 g) in 1,4-dioxane (30 mL) was added triethylamine (8-50 mL) and phosphorous oxychloride (7.4 mL). The reaction was heated under nitrogen at 100°C for 2 hr. The reaction mixture was cooled in an ice bath then treated successively with water and aq. sodium bicarbonate solution (final pH 8). Dichloromethane was added and the mixture was washed three times with water. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to a dark brown oil. The crude resultant was purified by silica gel chromalography using 30% ethyl aceiate in hexanes as eluani, providing 5b (3.8g, 70%) as a white solid. LC/MS: J 82.0 (MIT) Bromine (0.51 mL) was added to a solution of 5b (1.5 g) in 1:1 methanolAvater (40 mL) at -10 °C. After 10 min, the mixture was filtered to collect the precipitate that had formed. The filter cake was washed with cold MeOH/HjO (1:1) until the nitrate ran clear and was then dried under vacuum to yield 5c (3.0 g) as an off-white solid, which was used immediately without further purification. Step 5D: To compound Sc (prepared above) was added (RS) methyl 2-amino butyrate hydrochloride (1.3 g) followed by acetonitrile (40 mL) and 4 angstrom molecular sieves. The reaction mixture was heated at 110 °C for 5 h. Ethyl acetate and aq. sodium bicarbonate were added to the cooled reaction mixture, then the organic layer was washed three times with brine. The organic layer was dried over magnesium sulfate, filtered, and evaporated to give a crude yellow solid. Purification by silica gel chromatography using 30% ethyl acetate/hexanes as eluant provided 5d (800 mg, 28%) as an off white solid. EXAMPLE 6 S YNTHESIS OF REAGENT N-HYDROXY-ACETAMIDINE (Figure Removed) Sodium hydroxide (39 g of a 50% aq. solution) was added to a suspension of hydroxylamine hydrochloride (34 g) in methanol (100 mL) at RT. Acetonitrile (20 g) was added and the mixture was heated at 60 °C for 15 hr. The mixture was cooled and the solvents evaporated, then 300 mLethanoI was added to the residue. The solid was filtered off and rinsed with 200 mLethanoI, then the filtrate was evaporated to a vojume of 75 mL, The resulting precipitate was collected by filtration, rinsed with ethanol, then dried under vacuum to provide acetamide oxime Sa (19.5 g) as a white solid. Also prepared by this method were: 6b: propionamide oxime and 6c: buiyramide oxime. EXAMPLE? SYNTHESIS OFREAGEKT 2,2,2-TRiFLUoRO-N-HYDROxv-ACETAMTDavE (Figure Removed) Sodium methoxide solution (35.9 mL of a 25 % w/w solution in methanol) was added to a suspension of hydroxylamine hydrochloride (10.9 g) in methanol (200 mL) at RT. The mixture was stirred for 10 min then filtered, and the solid was rinsed with methanol. The filtrate was cooled and stirred in an ice bath, then trifluoroacetonitnle gas (16.7 g) was bubbled into the solution over 30 min. The reaction mixture was allowed to warm to RT then was evaporated to a volume of 1OO mL and filtered to remove solids. The tiltrate was evaporated to provide a crude waxy solid (18 g). A portion of this was funher purified by bulb-to-bulb vacuum distillation, affording Cmpd 7 as a tan waxy solid. EXAMPLE 8 S YI^THESIS OF REAGENT (S)-4,4,4-TRrFI-UORO-3-METHYL-BUTYRIC ACED ETHYL ESTER (Figure Removed) (R)-alpha-methyl benzylamine (16.0 g) was added to a solution of ethyl 4,4,4-trifluorobutyrate (24.4 g) in toluene (75 mL). p-Toluenesulfonic acid hydrate (630 mg) was added, and the mixture was heated to reflux with removal of water via Dean- Stark trap. After 2 hr, the mixture was cooled, ethyl acetate (100 mL) was added, and the solution was washed with aq sodium bicarbonate followed by brine. The organic layer was dried over sodium sulfale. filtered and evaporated to a yellow oil The oil was subjected to vacuum distillation (collection at 102-110 °C, ca. 5 mm Hg), providing 17.5 g of Cmpd 8a as a colorless oil. Step 8B: DBU (IS.] rnL) was added to 8a (17.44 g), and the brown mixture was heated at 70 °C for 12 hr. The cooled mixture was applied to a plug of silica gel, eluting wiih 4:1 hexanes/ethyl acetate to provide Cmpd 8b (14.5 g) as a yellow oil. S4ep 8C: Hydrochloric acid (7.0 mL, 2N) was added to a solution of Cmpd 8b (800 mg) in ether (10 mL). The mixture was stirred vigorously at RT for 15 hr, then the layers were separated. The aqueous layer was washed three times with ether then was evaporated to dryness. The residue was co-evaporated twice with toluene, then dried under vacuum to provide Cmpd 8c (410 mg) as a gum. EXAMPLE 9 SYNTHESIS OF REAGENT S-AMINO-PENTANWC ACID METHYL ESTER Benzylamine (2.51 mL) was added to a solution of methyl trans-2- pentenoate (2 62 g) in methanol (10 mL). The reaction vessel was sealed and the solution was heated at 85 °C for 3 hr. The solvent was evaporated, and the residue was chromatographed on silica gel, eluting with 3:1 hexanes/ethyl acetate to provide 9a (2.9 g) .3 g), 20% palladium hydroxide on charcoal (530 mg), and ethanol (10 mL) was stirred at RT under a hydrogen atmosphere (1 atm, baJloon) for 17 hr. The reaction mixture was sparged with nitrogen then filtered and evaporated. The residue was dissolved in DCM, dried over sodium sulfate, filtered and evaporated to provide Cmpd 9b (1,7 g) as a colorless oil, contaminated with approximately 20% of the corresponding ethyl ester. EXAMPLE 10 SYNTHESIS OF REAGENT (S)-NORVAUNE METHYX ESTER HYDRLCHXOKJDDE (Figure Removed) Acetyl chloride (3.0 mL) was added to methanol (60 mL) with stirring in an ice balh. (S)-norvaline (3.0 g) was added to the methanol solution, and the mixture was heated to reflux for 19 hr. The cooled solution was evaporated to dryness, then the residue was co-evaporated three times with toluene, then dried under vacuum lo provide Cmpd 10 (4.3 g) as a whtle solid. EXAMPLE 11 SVKTKESIS OF f l-(3-CYCLOPROPYL-[l ,2,4]OXADlAZOL-5-YL)-PROPYL]-[3-(4-METHOXY-2- lMETI•^YL-PHE^m-)-2,5-Drr£TOYL-PYRAZOLO(l>5-A|PYMIDIN-7-YL]-AMI^rE Step 11 A: fRS)-Methyl-2-aminobutyrate hydrochloride salt (0.81 g) was added to a solution of Cmpd 4d (0.800 g) in anhydrous acetonitrile (4 mL). Triethylamine (0,74 mL) was added, and the mixture was heated in a sealed tube in a microwave reactor at 150 °C for 35 min. The solvent was evaporated, then the crude residue was purified by silica gel chromatography using 2:1 hexanes/ethyl acetate as eluant to provide Cmpd lla (0.585 g, 58%) as a slightly yellow solid. Step 1IB: Sodium hydride (7 mg of a 60% suspension in mineral oil) was added to a suspension of N-HydroxycyclopropanecarboxamJdine (20 mg) in anhydrous THF (1 mL). The mixture \vas stirred at RT for 45 min, then a solution of Ha (50 mg) in anhydrous THF (0.5 mJL) was added, and the mixture was heated at 75 °C for I hr. The mixture was cooled and concentrated, then the residue was purified by silica gel chromaiography, using 2:1 hexanes/ethyl acetate aseluant lo provideCmpd 11-1 (20 mg) as a yellow oil. Depending on the pyrazolo-[l,5a]-pyrimidine, amino acid ester and oxime reagent, the compounds in the following table were prepared: (Table Removed) EXAMPLE 12 SYNTHESIS OF (3-(4-M.ETHOXY-2-METHYL-PHENYL)-2,5-DTHETHyL-PYR A2OLO[1,5- AlPYRIMIDIN-7-YL]-( I -METHYL-2-(3-METHYL-f J ,2,4]OXADJAZOL'5-YL)-ETHYL]-AMINE Step 12A: (R.S)-Ethy! 3-aminobutyrate (150 mg) was added to a solution of 4d (150 mg) in anhydrous acetonitrile (0.75 mL). The mixture was heated in a sealed tube in a microwave reactor at 150 °C for 35 min. The solvent was evaporated, then the crude residue was purified by silica gel chromatography using 2:1 hcxanes/ethyi acetate as eluant to provide Cmpd 12a (170 mg, 76%) as a yellow oil. Siepl2B: Sodium hydride (21 mg of a 60% suspension in mineral oil) was added to a suspension of acetamide oxime (60 mg) in anhydrous THF (2 mL) at RT. The mixture was stirred ai RT for 45 min, then a solution of 12a (160 mg) in anhydrous THF (1.6 mL) \vas added, the reaction vessel was sealed and the mixture was heated at 80 "C for 1.5 hr. The mixture was cooled and concentrated, then the residue was purified by silica gel chromalography, using 1:1 hexanes/ethy) acetate as eluant to provide 12-1 (72 mg) as a dark ye I low oil. Depending on the pyrazolo-[l,5a]-pyrimidine, arnino acid ester and oxime reagent, the compounds in the following table were prepared: (Table Removed) EXAMPLE n SYNTHESIS OF [3-(4-METHOXY-2-METHYL-PHENYL)-2,5-DIMETHYL-PYRAZOLOlJ ,5- A]PYRIMIDlN-7-YL)-[(S)-l-(3-METHYL-[l,2,4]OXADIA20L-5-Yl.)-BUTYL]-AMINE Step 13A: A mixture of compounds 10 (416 mg) and 4d (500 mg,), triethylamjne (0.35 mL) and acetonitrile (4 mL) was heated at 150 °C in a microwave reactor for 35 min. The mixture was partitioned between ethyl acetate and aq. sodium bicarbonate, then the organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was chromaiographed on silica gel, eluting with 4:1 hexanes/ethyl acetate to provide 13a (340 mg) as a yellow oil. Step 13B: Lithium hydroxide hydrate (44 mg) was added to a mjxiurt of Cmpd 13a (320 mg), THF (2 mL), and water (1 mL). The mixture was stirred vigorously at RT for 30 min, then hcxanes (5 mL) was added. The layers were separated and the aqueous layer was acidified with 2N hydrochloric acid (0.6 mL, final pH 3-4). The resulting precipitate was collected by filtration, washed with waier, co-evaporaied with toluene, then dried under vacuum to provide Cmpd 13b (215 mg) as a white solid. Step I3C: A mix(ure of 13b (160 mg), HOBT (79 mg), acetamide oxime (47 mg), DCM (2 mL), and DMF (0.25 mL) was cooled to -15 °C. DIG (0.085 mL) was added and the mixture was allowed to warm to RT over 2 hr. The solvents were evaporated, then ethyl aceiate (50 mL) was added and the mixture was washed once with saturated aq. sodium bicarbonate, then once with 10% aq. potassium dihydrogen phosphate. The ethyl acetate layer w,is dned over sodium sulfate, filtered, and concentrated to provide Cmpd 13c. Step 13D: Pyridine (1.5 mL) was added to Cmpd 13c prepared in the previous step, then the mixture was heated in a sealed tube at 100 °C for 2.5 hr. The solvent was evaporated. The residue was taken up in ether then filtered to remove DIU, nnsing with several portions of ether. The filtrate was evaporated, then the residue was chromatographed on silica gel, eluting with 3:1 hexanes/ethy] aceiate to provide Cmpd 13- 1 as a yellow oil. The free base 13-1 (115 mg) was dissolved in ether (2 mL), then 2 M HCI in ether (0.205 mL) was added at RT, resulting in formation of a white precipitate. The supernatant was decanted, the remaining solid was washed cwice with ether. Drying under vacuum ai 35 °C gave 13-1 hydrochloride salt (121 mg) as a white solid. Depending on the pyrazolo-[l,5a}-pyrimidine, amino acid ester and oxime reagent, the compounds in the following table were prepared: (Table Removed) EXAMPLE 14 SYTfTHESIS OF [3'(4-M£THOXY-2-METHYL-PIiENYL)-2,5-DIMETHYL-PYRAZOLO[],5- A)PWINtlX'!N-7-YL]-[(S)-1-(3-NQiTHYL-(I12,4]OXAOIA20L-5-YL)-PROPYL]-AMINE A suspension of sodium bicarbonate (28.7 g) and (S)-2-aminobutyric acid (21.7 g) in water (250 mL) was added to a solution of 4d (39.7 g) in dioxane (250 mL). The mixture was stirred and heated to reflux (102 °C barh) for 14 hr. The mixture was cooled lo RT, then concentrated HO (16 rnL) was added over 10 min to final pH 4.5. A copious white precipitate formed. The mixture was concentrated to a weight of about 250 g, then the residue was subjected to co-evaporation with several ponions of ethyl acetate, resulting in a thick, pasty aqueous slurry. The mixture was filtered, and (.he filter cake was washed with water (total 350 mL). The filter cake was then dried under vacuum at 35 °C, i yielding compound 14a (45.2 g) as a white solid. Alternate Step 14 A: NaHC03 (97,45 g, 1.16 mol) and (S)-2-arninobutyric acid (74.25 g, 0.72 mol) were suspended in water (900 mL). To this was added a solution of chjoropyrimidine 4d (134.4 g) in dioxane (900 mL) and the resulting mixture warmed to reflux and stirred for.2.5 h. The mixture was cooled to rt, and acidified to pH 4 with adding cone. HC1 (approx 88 mL) dropwise forming a copious white precipitate. The mixture was concentrated in vacua and the resulting solid slurried in water (1L), stirred and filtered, washing with water. More product precipitate was observed from the mother liquors and two more crops were obtained. The combined solids were dried in vacua to give to desired carboxylic acid 14a as a cream colored solid (159.3 g, 0.4 mol, > 93 % purity). In an alternate workup, the reaction mixture is filtered immediately following acidification with the cone. HCI and the solid is dissolved in methylene chloride The remaining water in the solid was separated and removed and the meihylene chloride layer was dried and concentrated to give 14a. Step t4B: Cmpd 14a (10 g) was suspended in toluene (50 mL) and evaporated to dryness. Dry DCM (100 rr)L) was added followed by HOBT (4.8 g) and acetamide oxime (2.7 g). Anhydrous DMF (II mL) was added, thei\ the reaction mixture -was stirred and cooled in an ethylene glycol/dry ice bath to an internal temperature of -15.5 °C under a nitrogen atmosphere. DIG (5.3 mL) was then added via syringe. The reaction mixture was stirred and allowed to warm over 2 hr, at which time the internal temperature was +16.5 °C. The solvents were evaporated, then ethyl acetate (150 mL) was added and the mixture was washed once with 10% aq. potassium dihydrogen phosphate, twice with saturated aq, sodium bicarbonate, once again with 10% aq. potassium dihydrogen phosphate, and finally with brine. The ethyl acetate layer was dried over sodium sulfate, Filtered, and concentrated to provide crude Cmpd 14b. Alternate Step I4B: Compound 4a (411.91 g, 0 95 mol) was suspended in CH2CHZ (3.8 L) and DMF (300 mL), to which was added aceiamidoxime (95.12 g, 1.28 mol) and HOBt (167.56 g, 1.24 mol) under a nitrogen atmosphere. The mixture was cooled to an internal temperature of -30 °C and DIG (194.J5 mL, 1.24 mol) was added dropwise so as to maintain the temperature below -20 °C. The reaction was stirred at this temperature for 1 hour and subsequently allowed to warm to 10 °C over the next 3 hours. The mixture was concentrates! in vacua and redissolved in EtOAc (5 L). The EtOAc solution was washed with NaHCOj (3 x 1.5 L, sat. aq.), KH2PO4 (1500 mL, 1M), brine (2 x 1.5 L), dried (Mg$C4) and concentrated in vacua to give 14b as a yellow foam. Step I4C: Pyridine (50 mL) was added to Cmpd 14b from Step 14B. then the mixture was heated under nitrogen at 100 °C for 4 hr. TKe resulting solution was allowed to cool, the solvent was evaporated, and the residue was co-evaporated twice with ethyl acetate and once with heptane. The residue was taken up in 50 mL ether, then filtered to remove DITJ, rinsing with several portions of ether. The filtrate was evaporated, then the residue was chromatographed on silica gel, cluting with 2:1 hexanes/ethyl acetate to provide the partially purified Crnpd 14-1 as a slightly yellow foam. The foam was co-evaporated twice with heptane, then 5:1 heptane/ethyl acetate (60 mL) was added, and the resulting slurry was stirred at RT for 24 hr. The solid was filtered and rinsed with hexanes, providing 14-1 free base (7.3 g) as a white solid. The filtrate was concentrated and a second crop of 14-1 fire base (0.7 g) was collected, also as a white solid. The free base 14-1 (6.0 g) was dissolved in 80 mL acetone and cooled in an ethylene glycol/dry ice bath to -12 °C (internal). Hydrogen chloride (8.9 mL of a 2.0 M solution in ether) was added in one portion. The clear yellow solution was stirred for 1 min, then the solvent was evaporated. The residue was co-evaporated with two portions of acetone, then dried under vacuum to produce an amber foam. The foam was pulverized and then dried under vacuum at RT for 24 hrv providing the hydrochloride salt 14-1 (6.7 g) as an amorphous tan powder. Alternate Step 14C: Compound 4b from alternate Step 14B was dissolved in pyridine (1,8 L), warmed to 100 °C, stirred for 2 hours and then was concentrated in vacuo to give a brown viscous oil. Purification by flash chromatography eluting with EtOAc:hexane (1:9, 2:8, 3:7, 4:6) gave a cream colored solid. This solid was slurried in heptane (4 L) and ground to a fine powder by stirring to give 14-1 as a white crystalline solid (248.5 g, 98.3 % purity). Depending ort the pyrazo)o-[l,5aj-pyrimidine, amino acid ester and oxime reagent, the compounds in the following table were prepared: (Table Removed) EXAMPLE 14A CHARACTERIZATION OF POLYMORPH FORM 1 oF(3-(4-METHOXY-2-METHYL-PHENYL)-2,5- DIMETHYL-PYR AZOLOf 1,5-A]PYRIMIDlN-7-YL}-[(S)-1 -(3-METHYL-[ 1,2,4)OXAr>lA2OL-5-YL)- PROPYL]-AMINE Free Base 14 -1 prepared as shown in alternate Step 14C affording 248.5 g of 14-1 may be characterized by, for example, X-Ray powder diffraction speccrometry, Raman specirometry and/or Differential Scanning Calonmetry (DSC), Free base of 14-1 shows the XPRD pattern of Figure J and was identified as polymorph Form 1 of [3-(4- Methoxy-2-methyI-phenyl)-2,5-dimethyl-pyra20lo(l,5-a3pyrimJdin-7-ylj-[(S)-l-(3- methyi-[ 1,2,41oxadiazol-5-y])-propy]]-amine. Table 1 shows the XRPD angles and d spacings for polymorph Form I of [3-(4-N'Iethoxy-2-methyl-pheny])-2,5-dimethyl pyra2o!o[l,5-a)pyrimidin-7-yl]-[(S)-l-(3- methyl-[l,2,4]oxadiazol-S-yl)-propyr)-armne. (Table Removed) The X-ray powder diffraction pattern of polymorph Form 1 as shown in Figure 1 exhibits predominant peaks (expressed in degrees 19 (+1- 0.15 degrees 19) at one or more of the following positions: 6.721, 11.757, 13.323, 18.222, 21.426 and 21.974. More specifically, such characteristic peaks are at 11.757 and 21.974, and further at 6.721 and further at 13.323, 18.222, and 21.426. Description of Figures: Figure I shows X-Ray powder diffraction data obtained for polymorph Form 1 of [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]- ((S)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propylJ-amine as described before. Form 1 is characterised by having an XRPD pattern with signals substantially as listed in Table 1. Figure 2 shows the Raman spectrum of polymorph Form 1 of [3-(4- Metho>cy-2-methyl-phenyI)-2,5-dimethyl-pyrazolo(l,5-a]pyrimidin-7-yl]-[(S)-l-(3- methyl-[l,2,4]oxadia2ol-5-yl)-propyI]-amine. Figure 3 shows a Differential Scanning Calorimetry (DSC) thermogram of polymorph Form 1 of (3-(4-Methoxy-2-methyI-phenyl)-2,5-dimethyl-pyrazolo[l,5- a]pynmidin-7-yl]-[(S)-l-(3^methyl-(l,2,4]oxadiazol-5-yl)-propyl]-anijne. It will be recognised that spectra and diffraction data will vary slightly according to various factors such as the temperature, concentration and instrumentation used. The skilled person will recognise that XRPD peak positions are affected by differences in sample height. The peak positions quoted herein are thus subject to a variation of +/- 0.15 degrees 2-theta. As shown in Figure 3, the polymorph Form 1 exhibits a predominant endotherm peak at about 108.3 °C. It should be recognized that that the endotherm peak as measured is dependent under a number of factors including the machine employed, the rate of heating, the calibration standard, humidity and the purity of the sample used. Accordingly, the term "about 108.3 °C" is intended to encompass such instrument variations, X-Ray Powder Diffraction X Ray Powder Diffraction (XRPD) analysis was performed on Broker D5005, using Soi-X detector. The acquisition conditions were: radiation: Cu Ka, generator tension: 40 kV, generator current: 50mA, start angle: 2.0 °20, end angle: 45.0 °26, step size: 0.02 °28 , time per step: 0.5 seconds. The sample was prepared on zero background sample holder. Rainan Speciroscopy Instrument Configuration: Kaiser RXN1 Kaiser Optical System Micro Raman. Sample on Al sample pan, laser I = 785nm. Differen* al Scanning Calorimetry (DSC) Instrument configuration: PE DSC 7, not ermetic sample pan, run @ 1 QKJmin to J 50 °C, sample 1.5-5 mg. EXAMPLE 14B SYNTHESIS AND CHARACTERISATION OFPOLYMORPH FORM 2 OF [3-(4-METHOXY-2- METHYL-PHENYL)-2>5-DrMETHYL-PYR AZOLO[ 1 ,5-A]PYRIMTDIN-7-YL]-[(S 1 -(3-METHYL- [ 1 ,2,4)OXADlA20I.-5-Yi.)-PROPYL]-AMINE Polymorph Form 2 of {3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethylwas prepared as follows: [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimelhyl-pyTa2olo[l,5-a]pyrimidin-7- yl]-[(S)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-aminepolymorph Form I (0.74 g) was slurried in 50% aqueous isopropanol (4rnL). The temperature was cycled between 0 and 40 °C for 24 hours, then the mixture stirred at ambient temperature for 3 days, then the ott and dried at ambient temperature to give 0.70 g of (3-(4-Methoxy-2-methy!-phcnyl)- 2,5-dimethyl-pyrazolo[l,5-aJpTimidin-7-yl]-[(S)-!-(3-methyl-[1.2,4]oxadiazol-5-yl)- propyl)-amine polymorph Form 2. Preparation of polymorph Form 2 of [3-(4-Methoxy-2-meihyl-phenyl)-2,5- dimethyl-pyrazo!o[l>5-a]pyrimidin-7-yl]-[(S)-J-(3-methy]-[l,2,4]oxadiazol-5-yl)-propyl]- amine was repeated on large scale as follows. Free Base 14-1 was prepared in an analogous way as described before in EXAMPLE 14, except for the lack of the chromatographic purification present in Step 14C. The formation and successive liberation of the mesylate salt afforded a desired compound with a high purity without the necessity of a chromatography. Free Base 14-1 (2.48 kg, 6.10 mol, chemical purity 90%) was stirred with n-Butyl acetate (12.5 L) for 30 to 45 minutes then Methane sulphonic acid (1.2 eq, 7.32 Mol, 703 g) was added. After stirring for 2-3 hrs at 25-30 °C the mixture was filtered. The solid was slurry washed with n-Butyl acetate (5 L) followed by Heptane (7.5 L). then dried for 4-6hrs at 50±5 °C under vacuum to give Mesylate salt (2.48 kg, chemical purity 97.37%). The mesylate salt was stirred with DM water (1.2.5 L) for 15 to 30 minutes. Aq. ammonia was added to a pH of 9.0-10. The suspension was extracted with ethyl acetate (3 x 7.5 L). then the combined extracts were washed with DM water (5 L) and 20% Brine solution (5 L). The organic solution was concentrated under vacuum at below 50±5 °C, removing 85 to 90 % of the solvent, then the residue cooled to 30±5 °C. Heptane (15 L) was added and the mixture stirred for 2 to 3 hrs at 25-30 °C then 60 to 70 % nf the solvent was distilled off under vacuum at below 50±5 °C. The mixture was cooled to 30±5 °C, stirred for I to 2 hours, then filtered. The solid was slurry washed with Heptane (5 L) then dried under vacuum at below 50±5 °C to give polymorph Form I of [3-(4- melhoxy-2-methyl-phenyl)-2,5-dimcthyl-pyrazolo[l>5-a]pyrimidin-7-yl]-i(S)-l-(3-methyl- [l,2,4joxadiazol-5-yl)-propyl]-amJne (1.70 kg, chemical purity 99.34%). A mixture of polymorph Form 1 (1.37 kg, 3.37 Mol, purity by HPLC 99.34%) of |3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyI-pyrazolo[l,5-alpyrimidin-7- yl]-[(S)-l-(3-mcthyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine and ethyl acetate (2.05 L) were heated to 40 to 45 °C (a clear solution was observed). The solution was then cooled to 30±5 °C and Heptane (6.85 L) added before heating to 60±2.5 °C. Polymorph Form 2 of p-(4-me(hoxy-2-methyl-phenyl)-2,5-dimeihyl-pyrazolon,5-a]pyrimidin-7-yl]-[(S)-l-(3- methyl-[l,2.4]oxadiazol-5-y!)-propyl]-amine seed material prepared as described above (0.5% w/w) was added at 60±2.5 °C then the mixture was cooled to 40±2.5 °C, then healed back to 50±2.5 °C when further seed material (0.5% w/w) was added. The resulting slurry was cooled to 30±5 °C and stirred for 12 hrs at 30±5 °C. Heptane (2.74 L) was added and the mixture stirred for a further 12 hrs at 30±5 °C. The slurry was filtered and the solid slurry washed with Heptane (2.74 L). The solid was dried under vacuum at 50±5 °C for 8hrs to give 0.97 kg of polymorph Form 2 of f3-(4-methoxy-2-methyl-pl:e.nyl)-2,5- dimethyl-pyra2olofl,5-a]pyrimidin-7-yl)-((S)-i-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]- amine (HPLC purity 99.58%). HPLC method Column : Zorbax SB-C18(l50x4.6 mm), 3.5 micron Mobile Phase-A : 0.05% TFA(Aqueous) Mobile Phase-B : 0.025% TFA(Acetonitrile) Column temperature : 40 °C Flow rate : I.OrrJ/min Wavelength of detection : 225nm Injection volume : 5)4.1 Run time : 30 mins Concentration : 0.3 mg/ml Gradient program : Linear gradient Time in min Mobile phase-A(%) Mobile phase-B (%0 75 25 25 5 95 29 5 95 30 75 25 Post run time : 5 min Retention time ; Form 2 about 9 min Diluent: Mobile Phase-A: Mobile Phase-B (1:1) Polymorph Form 2 of [3-(4-methoxy-2-methyl-phenyl)-2,S-dimethylpyrazolo{ t,5-a]pynmidin-7-yl]-[(S)-l-(3-methyi-[i,2,4]oxadiazol-5-yl)-propyl]-amine shows the XPRD pattern (Figure 4). Table 2 shows the XRPD angles and d spacings for polymorph Form 2 of[3-(4-Methoxy-2-methyl-iphenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-l- (3-methyI-[J,2.4]oxadiazoJ-5-yl)-propyl]-amine. Figure 4 shows X-Ray powder diffraction data obtained for polymorph Form 2 of [3-(4-Meihoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrirnidin-7-yl]- [(S)-H3-methyl-[l,2,4]oxadia7,ol-5-yl)-propyl]-arnine as described before. Form 2 is characterised by having an XRPD pattern with signals substantially as listed in Table 1. Figure 5 shows the Raman spectrum of polymorph Form 2 of (3-(4- Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimJdin-7-yl)-[(S)-]-(3- methyl-[ I ,2,4]oxadiazol~5-y])-propyl]-amine. Figure 6 shows a Differential Scanning Calorimetry (DSC) thermogram of polymorph Form 2 of p-(4-Methoxy-2-methyl-phenyl)-2,5-dirnethyl-pyrazo!o[l,5- a]pyrimidin-7-yij-[(S)-l-(3-methyl-[l,2,4]oxadJazol-5-yl)-propyl]-amine. It will be recognised thai spectra and diffraction data will vary slightly according to various factors such as the temperature, concentration and instrumentation used. The skilled person will recognise that XRPD peak positions are affected by differences in sample height. The peak positions quoted herein are thus subject to a variation of+/- 0.15 degrees 2-theta. As shown in Figure 6. the polymorph Form 1 exhibits a predominant endotherm peak at about 115.1 °C. Il should be recognized that that the endotherm peak as measured is dependent under a number of factors including che machine employed, the rate of heating, the calibration standard, humidity and the purity of the sample used. Accordingly, the term "about 115.1 "C" is intended to encompass such instrument variations. X-Ray Powder Diffraction X Ray Powder Diffraction (XRPD) analysis \vas performed on Bruker D5005, using Sol-X detector. The acquisition conditions were: radiation: Cu Ka, generator tension. 40 kV, generator current: 50mA, start angle: 2.0 °29, end angle: 45.0 °26, stfip size: 0.04 °29 , time per step: 1 second. The sample was prepared on zero background sample holder. Raman Spectroscopy Instrument Configuration: Kaiser RXN1 Kaiser Optical System Micro Raman. Sample on Al sample pan, laser J = 785nm, Differential Scanning Calorimelry (DSC) Instrument configuration: Q 1000 TA, not ermetic sample pan, run @10K/min to 150 °C, N2 Flow =50mL/min, sample 1.5-5 mg. EXAMPLE J5 SYNTHESIS OF [ 3-(2,4-DlMB™OXY-ra£NYL)-2,5-DIMETOYL-PYRAZOLO[ 1,5-A]PYTUMIDrN-7- YL]-(2-METHOXY-ETOYL)-(3-METHYL-[l,2,4}OXADt.AZOL-5-YLVIETHYL)-AMrNrE DBU (Figure Removed) Step 15A: To a solution of 2-methoxyelhylamine (2.9 mL) in THF (40 mL) was added tri ethyl ami ne (9.3 mL) followed by methyl bromoacetate (2.8 mL). The mixture was stirred ai RT for 16 hr, then the solvent was evaporated. The residue was dissolved in ethyl acelate (100 mL), washed with water (2x 50mL), brine (50 mL), then the organic layer was dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography using 95:5 dichloromethane/methanol as eluant to give ISa (1.8 73 g, 37 % yield) as a colorless liquid. 1H NMR (CDC13, 300 MHz): 2.78 (t, 2H, J=3Hz), 3.33 (s, 3H), 3.43 (s, 2H), 3.48 (t, 2H, J=3Hz), 3.70 (s, 3H). Step I SB: DBU (0.22 mL) and Cmpd 15a (220 mg) were added to a solution of Cmpd 4e (400 mg) in acetonitnle (4 mL). The solution was stirred and heated at 80 °C for 16 hr. The cooled mixture was concentrated, then ethyl acetate (20 mL) was added. The mixture was washed with water (2x lOmL), then brine (10 mL), and the resulting organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using 95:5 dichloromethane/methanol as eluant to provide Cmpd ISb as an oil. Mass: 428.8 (MPT); HPLC: Analytical Method 2, retention time 1,46 rain. Step 15C. A suspension of acetamide oxime (60 mgin anhydrous THF (5 mL) was stirred at RT as NaH (32 mg of 60% dispersion in oil) was added. The mixture was stirred for 45 min at RT, then a solution of Cmpd ISb (J73 mg) in anhydrous THF (5 mL) was added. The mixture was refluxed for 2 hr. The cooled mixture was concentrated, then taken up in ethyl acetate (10 mL) and washed with water (2x 10 mL) and brine (10 mL). The resulting organic layer was dried over magnesium sulfate, filtered, and evaporated. The residue was purified by preparative LC/MS to provide Cmpd 15-1. Mass: 452.8 (MH*). HPLC: Analytical Method 2, retention time 1.406 nun. Depending on the pyra2olo-[l,5a]-pyrimidine, amino acid ester and oxime reagent, the compounds in the following table were prepared: EXAMPLEJ6 SYNTHESIS OF f3-(2,4-DrMETMOXY-PHENYL)-2,5-DiMEnrYL-PYRAZoi.o[ l,5-A]pYRiMiDrN-7- Srep J6A: To Cmpd 4e (200 mg) in acetonitrile (5 mL) was added 2- methoxyethylamine (2 mL). The solution was stirred and heated at 80 °C for 16 hr. The mixture was concentrated under vacuum. The residue was dissolved in ethyl acetate (5mL), and the resulting solution was washed with water (2x 5mL) and brine (5 mL). Drying over magnesium sulfate, filtration, and concentration provided a yellow oil, Cmpd 16a, which was used in the following step without purification. Sodium hydride (76 mg of a 60% dispersion in oil) was added.to a solution of 16a prepared in Step 16A in DMF (5 mL). After 5 minutes at RT, methyl 4- bromobutyrate (0.21 mL) was added. The mixture was heated for 48 hr at 60 °C in a sealed vial. The cooled mixture was concentrated, taken up in ethyl acetate (25 mL) and washed successively with water (2x 10 mL) and brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The crude residue 16b was used without further purification. Step lPL: Crude Cmpd 16b, prepared above in Step 16B. was subjected to the procedure of Step 15C. The crude reaction mixture was diluted with methanot, then purified directily by preparative LC/MS to afford Cmpd 16-1. Mass: 480.8 (MH*); HPLC: Analytical Method 2, retention time 1.353 min. EXAMPLE 17 SYNTHESIS OF (3-(4-METHOXY-2-METHYL-WEmX)-2,5-DIMETHyL-PYRA20LO[ 1,5- A]PYRIMTDIN-7-YL]-[(R)-l-METHYL-2-(5-METHYL-[l,2,4]OXAI>IAZOL-3-YL)-ETHYL]-AKaNE Step 17A: A mixture of Cmpd 4d (1.0 g), (R)-2-am1no-l-propane! (0.5 g), triechylamine (0.91 mL), and acetonitrile (5 mL) was heated with stirring at 90 °C for 4 hr. The reaciion mixture was partitioned between saturated aq. sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with one additional portion of ethyl acetate, then ihe combined organic layers were dried over sodium sulfate and concentrated to provide Cmpd 17a as a yelJow oil, which was used without further purification. Sier> 17B: A solution of methanesulfonyi chloride (0.68 g) in DCM (1.0 mL) was added dropwise to a stirred mixture of crude Cmpd I7a (prepared above), triethylamine (0.91 mL). and DCM. A clear brown solution resulted, and the mixture was stirred at RT for 30 mm. Saturated aq. sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate (2x 25 mL). The combined organic layers were washed once with potassium carbonate solution and were then dried over sodium sulfate. filtered, and concentrated to provide Cmpd 17b as a white foam. This material was used without further purification. Step 17C: Powdered sodium cyanide (0.33 g) and potassium carbonate (0.92 g) were added to a solution of Cmpd 17b (prepared above) in DMF (10 mL). The mixture was heated in a sealed tube at 100 °C for 4 hr, forming a thick gel. Saturated aq. sodium bicarbonate solution (25 mL) was added and the mixture was extracted with ethyl acetate (2x 25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 30% ethyl acetate in hexane as eluant, providing Cmpd 17c (0.72 g, 62% yield) as a slightly yellow oil. StejpJJD, A solution of Cmpd 17c (200 mg) in ethanol (4 mL) was treated with hydroxylamine hydrochloride (50 mg) and potassium hydroxide (40 mg). The mixture was stirred and heated at 100 °C in a sealed lube for 4 hr. The cooled mixture was filtered, and the filter cake was washed twice with 5 mL cold ethanol. The combined filtrates were concentrated providing Crnpd 17d as a white solid which was used without further purification. Step 17E: Cmpd 17d (prepared above) was dissolved in N,N-dimethylacetamide dimethylacetal (4 mL). The mixture was heated at JOO °C for 2 hr. The mixture was concemaraied and the residue was purified by silica gel chromatography, cluting with 30% ethyl acetate in hexane. The product was converted into the HCI salt following the. procedure of StegJ4C. 72 mg (28% yield). Depending on the pyrazolo-[l,5a]-pyrimidine, amino acid esier and oxi reagent the compounds in the following table were prepared: (Figure Removed) EXAMPLE 18 SYNTHESIS OF i(R)-2-(5-CVCtX)PROPYL-(l,2,4]OXADlAZX)L-3-yL)-l-METHYL-ETHYL]-p-(4- METHOXY 2-MJ.TOYL-PH£NYL)-2,5-DINlETHYl.-PYRAZOLO[l,5-A]PYRlMTDIN-7-YL]-AMINE (Figure Removed) Crude Cmpd I7d (100 mg) was dissolved in 2 mL pyridine and treated with cyclopropanecarbonyl chloride (0.024 mL). The mixture was heated in a sealed tube at 80 °C for 2 hr, then the solvent was evaporated and the residue was purified by preparative LC/MS. Depending on the pyrazo]o-[l,5a]-pyrimidine and carbonyl chloride reagent, the compounds in the following table were prepared: (Table Removed) EXAMPLE 19 SYNTHESIS OF (3-(4-METHOXY-2-METHVL-PKENYL)-2,5-r>rMETHYL-PYR/VZOLO[l,5- A]PYTllMroD^-7-yL]-[(S)-2,2>TT{lH,UOR04-(5-METHYL-[l>2,4}OXADlAZOL-3-YLMETHYL)- ETHYL]-AMINE Seep 19A: A mixture of 4d (565 mg) and 8c (400 mg) in acetonitrile (3.5 mL) was heated in a sealed tube in a microwave reactor at 150 °C for 30 min. Aqueous sodium bicarbonate solution was added, and the mixture was extracted once with 3:1 hexanes/ethyl acetate then once with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 3:1 hexanes/ethyl acetate as eluanl to provide 19a (410 mg, 53 %) as a slightly yellow oil. Step 19B: A mixture of!9a ( L . I g), lithium hydroxide (300 mg), THF (10 mL), and water (2 mL) was heated at 90 °C for 2 hr. The cooled reaction mixture was treated with 4M hydrochloric acid (5 mL) and water (25 mL). and the resulting mixture was extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfaie, tillered, and evaporated to provide crude 19b (J.I g) as a yellow oil, which was used without further purification. Step 19C: A solution of crude 19b (l.l g) in THF (10 mL) at RT was treated with oxalyl chloride (0.34 g), followed by iwo drops of DMF. Vigorous gas evolution was observed, and the mixture was stirred at RT for Ihr. The reaction mixture was concentrated, then ammonia (20 mL of a 2.0 M solution in djoxane) was added, and the resulting suspension was stirred at RT for 16 hr. Aqueous sodium bicarbonate solution was added, and (he mixture was extracted twice with ethyl acetate. ~'\e organic layers were combined, dried over sodium sulfate, filtered, and concentrated to provide 19c (700 mg) as a pale green oil. which was used without further purification. Step 19D: A solution of 19c (700 mg) and TEA (750 mg) in dioxane (10 mL) was treated at RT with trifluoroacetic anhydride (1.5 g). The reaction mixture was stirred at RT for 2 hr, then aq. sodium bicarbonate solution was added and the mixture was extracted twice with dichtoromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography, using 30 % ethyl acetate in hexanes as eluant, providing 19d (400 mg) as a yellow oil. Step I9E: To a solution of 19d (400 mg) in ethanol (10 mL) was added hydroxylamine hydrochloride (85 mg) and potassium hydroxide (70 mg). The mixture was heated at )00 °C for 4hr. The reaction mixture was cooled to RT and filtered, and the filter cake was washed with eihanol. The combined filtrates were concentrated, then the residue was dissolved in DMA-DMA (10 mL) and heated at 90 °C for 2hr. The reaction mixture was concentrated, and the residue was purified by silica gel chromatography, eiuurig with 3:1 hexanes/ethyl acetate to provide 19e free base (70 mg) as a yellow oil. The free base was dissolved in acetone (5 mL) and treated with hydrogen chloride (2 mL of 2,0 M solution in ether). The mixture was concentrated in vacua to provide 19-1 HCI /.i mgj as a yenaw solid. Mass: 461 .0 (MH*); HPLC: Analytical Method 1, retention lime 5.28 min. EXAMPLE 20 SYNTHESIS OF ETHYL-[3-(4i-METHOXY-2-METHYL-PHENYL)-2,5-DJMETH YL-PYRAZOLO( 1 ,5- A]PYRlMIDIN-7-YL]-(3-METHYL-[l,2,4jOXADIA20L-5-Yl_METHYL)-AMTNE Step 2QA; Thjonyl chloride (0.71 mL) was added carefully to a cold solution of Nethy) glycine (0 50 g) dissolved in anhydrous methanol (8 mL). The mixture was heated at 60 °C for 14 hr in a sealed tube. The mixture was concentrated then subjected to coevaporation with toluene (2x) and acetonitrile (3x). Drying under vacuum gave the arruno ester hydrochloride salt 2fla as a white gummy solid, which was carried on directly without further purification, Step 208: The condensation of Cmpds 20a and 4d by the procedure of Step !JA provided Cmpd 2flb (164 mg) as a yellow oil after silica gel chromatography. 83 Compound 20b (164 mg) was subjected to the procedure of Step J IB to afford Crnpd 20-1 (105 mg) as a slightly yellow oil after silica gel chromaiography employing hexanes/ethyl acetate eluant Depending on the pyrazolo-[l,5a]-pyrimidine, amino acid ester and oxime reagent, the compounds in the following table were prepared: All HPLC employed Analytical Method 1. EX AMPLE 21 SYNTHESIS OF t3-(4-METHOXY-2-WETHYL-PHENYL)-2,5-DrMETHYL-PYRA2OLO[l,5- A]PYRJ3vlIDtN-7-YL]-(i-[l,3,4]OXADJA2OL-2-yj--PROPYL)-AM£NE NH, Step 21 A: Hydrazine hydrate (0.50 mL) was added to a suspension of Cmpd lla (230 mg) in ethanol (1.5 mL) at RT. The reaction vessel was sealed and heated with stirring at 75 °C for 17 hi. The clear solution was cooled and concentrated to provide the hydrazide Cmpd 21a as an oil (230 mg). Step2!B: Crude 21a from the preceeding step (70 mg) was dissolved in ethyl formate (2 mL) and heated at 65 °C for 72 hr. The cooled solution was concentrated to provide the crude diacyl hydrazme Cmpd 21b (70 mg) as an oil. Step 21C: A rruxture of Cmpd 21b from the preceeding step (29 mg), ptoluenesulfonyl chloride (27 mg), DBU (0.053 mL), and THF (0.5 mL) was healed in a microwave reactor at 150 °C for 10 min. Aqueous sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by preparative thin-layer silica gel chromatography, eluting with 1:2 hexanes/ethyl acetace to afford Cmpd 21-1 as art oil (12 mg). Mass: 393.0 (Mlf); HPLC: Analytical Method 4, retention time 2.40 min. EXAMPLE 22 SYNTHESIS OF [3-(4-METHOXY-2-METHYL-PHENYL)-2,5-DIMETHYL-PYRAZOLO( 1,5- A)PYRJMron^.7-YL]-[l Compound lla was subjected to lithium hydroxide hydrolysis according to the procedure of Step 13C giving Cmpd 22a as a white waxy solid. Siep 22B: Compound 22a (100 mg) and N-acetylhydrazine were subjected to the procedure of S;ep 14B. The crude ethyl acetate extract was dried over magnesium sulfate, filtered, and concentrated to provide Cmpd 22b (110 rng, 96%) as a white solid. Step 22C: Compound 22b (50 mg) was subjected to the procedure of Step 2JC with healing in a microwave reactor at 150 °C for 15 min. The resultant was purified by preparative thin-layer silica gel chromaiography, elating with 48:48:4 hexanes/ethyl acetate/methanof to yield Cmpd 22-1 (8 mg, 71%) as a solid. Mass: 407.0 (WttT); HPLC: Analytical Method 1, retention time 4.543 min. EXAMPLE 23 SYNTHESIS OF [3-(4-METHOXY-2-METHYL-PH£NYL)-2,5-DIMETHYL-PYRAZOLO[l ,5- A]PYRlMJDtN 7-YL]-[l-METHYL-2-(5-ME-raYt-[l,3,4]OXAr>tAZOL-2-YL)-EniYLj-AMI>rE Scep23A: (RS)-Ethyl 3-aminobutyrate (435 mg) was added to Cmpd 4d (500 mg) according to the procedure of Step UA to afford Cmpd 23a (540 mg) after silica gel chromatography using 2:1 hexanes/ethyl acetate as eluant. Step 23B: Compound 23a (400 mg) was subjected to the procedure of Step 21A to afford Cmpd 23b (367 mg). Step 23C: A solution of Cmpd 23b (180 mg) and triethylamine (0.100 mL) in DCM (4 mL) was treated with acetic anhydride (0.53 mL) at RT. After 17 hr, additional triethylamine (G.IOO mL) and acetic anhydride (0.53 mL) were added. The solvent was evaporated, then aq. sodium bicarbonate solution was added and the mixture was extracted with DCM (4x 10 mL). The combined organic extracts were washed with bnne, dned over sodium sulfate, filtered, and evaporated. The residue was chromatographed on silica gel ehinng with 5% methanol in DCM to afford Cmpd 23c (165 mg). Step.23D; Compound 23c (50 mg) was subjected to the procedure of Step 21C substituting 1,3,4,6,7,S-hexahydro-l-me.thyl-2H-pyrimido[I,2-A]pyrimidine in place of DBU. Purification by preparative thin-layer silica gel chromatography (1:1 hexanes/acetone as eluant) provided Cmpd 23-1 (12 mg). Depending on the pyra2olo-[l,5a]-pyrimidine, amino acid ester and oxime reagent, the compounds in the following table were prepared: (Figure Removed) EXAMPLE 24 SYNTHESIS OF [3-(2-CHLORO-4-METHOXY-PHENVL)-2)5-DIM3rrHYL-PYRAZOLO[ 1,5- A]PYlUMJDlN-7-Yt]-[l-(3-METHYL-[l,2,4]OXADlAZOL-5-YL)-PROPYLl-AMINE Step 24A: To Cmpd Sd (100 mgl) was added 2-chloro-4-methoxypheny)boronic acid (70 mg) followed by potassium carbonate (80 mg) and a solution of dioxane/water (0.9 mL/0.2 rnL). The reaction mixture was sparged with nitrogen for 5 mjnv then tetrakisOnphenyphosphine)palladium(O) (80 mg) was added, and the reaction vessel was sealed and heated at 85°C for 16 hr. The solvent was evaporated, and the residue was purified directly by preparative thin-layer silica gel chromatography using 30% ethyl acetate in hexanes as eluant, providing Cmpd 24a as a solid (31 mg, 26%). LC/MS: 403.0 Compound 24a (31 mg) and acetamidoxime were subjected to the procedure of SlBb to afford Cmpd 24-1 (5.17 mg) after preparative thin-layer silica gel chromatography (1:1 hexanes/ethyl acetate eluant). Depending on the pyrazolo-[l,5a)-pyrimidine, amino acid ester and oxime reagent, the compounds in the following table were prepared: (Table Removed) EXAMPLE 25 CRP RECEPTOR BINDING ACTIVITY The compounds of this invention may be evaluated for binding activity to the CRP receptor by a standard radioligand binding assay as generally described by Grigoriadis et al. (Mol. Pharmacol vo!50, pp679-686, 1996) and Hoare et al. (Mol. Pharmacol vol may be used to evaluate the binding activity of the compounds of the present invention with any CRF receptor subtype. Briefly, the binding assay involves the displacement of a radiolabeled CRP ligand from the CRF receptor. More specifically, the binding assay is performed in 96- well assay plates using 1-lOu.g cell membranes from cells stably transfected with human CRP receptors Each well receives about 0.05 mL assay buffer (e.g., Dulbccco's phosphate buffered saline, 10 mM magnesium chloride, 2 mM EGTA) containing compound of interest. Or a reference ligand (for example, sauvagine, urocortin I or CRF), 0.05 mL of [USI] lyrosine - sauvagine (final concentration -150 pM or approximately the KD as determined by Scatehard analysis) and 0.1 mL of a cell membrane suspension containing the CRF receptor. The mixture is incubated for 2 hours at 22 °C followed by separation of the bound and free radioligand by rapid filtration over glass fiber filters. Following three washes, the filters are dried and radioactivity (Auger electrons from I251) is counted using a scintillation counter. All radioligand binding data may be analyzed using the non-linear least-squares curve-fitting programs Prism (GraphPad Software Inc) or XL/If (ID Business Solutions Ltd). EXAMPLE 26 CRF-STivruLATED ADENYLATE CYCLASE ACTIVITY The compounds of the present invention may also be evaluated by various functional testing. For example, the compounds of the present invention may be screened for GRF-stimulated adenylate cyclase activity. An assay for the determination of CRFstimulated adenylate cyclase activity may be performed as generally described by Battaglia et al (Synapse /:572, 1987) with modifications to adapt the assay to whole cell preparations. More specifically, the standard assay mixture may contain the following in a final volume of 0.1 ml: 2 mM L-glutamine, 20 mM HEPES, and 1 mM IMBX in DMEM buffer. In stimulation studies, whole cells with the transfected CRF receptors are plated in 96-well plates and incubated for 30 min at 37 °C with various concentrations of CRF-related and unrelated peptides in order to establish the pharmacological rank-order profile of the particular receptor subtype. Following the incubation, cAMP in the samples is measured using standard commercially available kits, such as cAMP -Screen™ from Applied Biosystems, For the functional assessment of the compounds, cells and a single concentration of CRF or related peptides causing 50% stimulation of cAMP production are incubated along with various concentrations of competing compounds for 30 min at 37°C, and cAMP determined as described above. It will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without departing from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims. WE CLAIM: l.A pyrazolo (1,5-alpha), pyrimidinyl compound represented by the following structure: (Formula Removed) or a pharmaceutically acceptable salt, solvate, stereoisomer thereof, R1 is hydrogen; R2a and R2b are independently hydrogen or C1-C6 alkyl; Y is a direct bond or -C(R4aR4b)- where R4a and R4b are each hydrogen; Het is (Formula Removed) R5 is C1-C6 alkyl or C1-C6 haloalkyl; R6 at each occurrence is independently C1-C6 alkyl; n is 1; Ar is phenyl; R7 at each occurrence is C1-C6 alkyl or C1-C6 alkoxy; o is 2. 2. A compound as claimed in claim 1, wherein: one of R2a and R2b is C1-C6 alkyl and the other is hydrogen; R5 is C1-C6 alkyl; and one R7 is C1-C6 alkyl and the other is C1-C6 alkoxy. 3. A compound as claimed in claim 1 or claim 2, wherein the compound is selected from the group of: [ 1 -(3-Isopropyl-[ 1,2,4]oxadiazol-5-yl)-propyl]-[3-(4-methoxy-2-methyl-phenyl)- 2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[l-(3-methyl-[ 1,2,4]oxadiazol-5-yl)-2-phenyl-ethyl]-amine; [ 1 -(3-Isopropyl-[ 1,2,4]oxadiazol-5-yl)-propyl]-[3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7-yl]-[ 1 -(3-methyl-[ 1,2,4]oxadiazol-5-yl)-butyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-(3-methyl-[ 1,2,4]oxadiazol-5-ylmethyl)-amine; (3-Isopropyl-[l,2,4]oxadiazol-5-ylmethyl)-[3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-l-methyl-2-(3-methyl-[l,2,4]oxadiazol-5-yl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[l-(3-trifluoromethyl-[ 1,2,4]oxadiazol-5-yl)-propyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-(3-propyl-[l,2,4]oxadiazol-5-ylmethyl)-amine; [2-(3-Ethyl-[ 1,2,4]oxadiazol-5-yl)-(R)-1 -methyl-ethyl]-[3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-amine; 3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-7-[(S)-2-(3-methyl-[l,2,4]oxadiazol-5-yl)-pyrrolidin-l-yl]-pyrazolo[l ,5-a]pyrimidine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[l-(3-methyl-[l,2,4]oxadiazol-5-yl)-ethyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[l-(3-methyl-[l,2,4]oxadiazol-5-yl)-butyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[3-methyl-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-butyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-methyl-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7-yl]-[ 1 -methyl-2-(3-methyl-[l ,2,4]oxadiazol-5-yl)-ethyl]-amine; Benzyl-[3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[2,2,2-trifluoro-l-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-ethyl]-amine; [2-(3-Isopropyl-[l,2,4]oxadiazol-5-yl)-l-methyl-ethyl]-[3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-amine; [2-(3-Isopropyl-[l,2,4]oxadiazol-5-yl)-(S)-l-methyl-ethyl]-[3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-l-methyl-2-(3-methyl-[l,2,4]oxadiazol-5-yl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7-yl]-[ 1-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-propyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7-yl]-[ 1-(3-methyl-[ 1,2,4]oxadiazol-5-ylmethyl)-propyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-butyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[2,2,2-trifluoro-(S)-1-(3-methyl-[ 1,2,4]oxadiazol-5-ylmethyl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[l-methyl-2-(3-trifluoromethyl-[l,2,4]oxadiazol-5-yl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-1 -methyl-2-(3-trifluoromethyl-[ 1,2,4]oxadiazol-5-yl)-ethyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7-yl]-[(R)-1 -methyl-2-(3-trifluoromethyl-[ 1,2,4]oxadiazol-5-yl)-ethyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yI]-[2,2,2-trifluoro-(S)-1 -(3-methyl-[ 1,2,4]oxadiazol-5-ylmethyl)-ethyl]-amine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[2,2,2-trifluoro-(S)-l-(3-trifluoromethyl-[l,2,4]oxadiazol-5-ylmethyl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7-yl]-[(R)-1 -(3-methyl-[ 1,2,4]oxadiazol-5-yl)-propyl]-amine; 3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-7-[(S)-2-(3-methyl-[1,2,4]oxadiazol-5-ylmethyl)-pyrrolidin-1 -yl]-pyrazolo[ 1,5-a]pyrimidine; [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazoIo[l,5-a]pyrimidin-7-yl]-(2-methoxy-ethyl)-(3-methyl-[ 1,2,4]oxadiazol-5-ylmethyl)-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-l-methyl-2-(5-methyl-[l,2,4]oxadiazol-3-yl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-1 -(5-methyl-[ 1,2,4]oxadiazol-3-ylmethyl)-propyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-1 -(5-methyl-[ 1,2,4]oxadiazol-3-ylmethyl)-propyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[ 1,5-a]pyrimidin-7-yl]-[(S)-1 -methyl-2-(5-methyl-[ 1,2,4]oxadiazol-3-yl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-1 -methyl-2-(5-trifluoromethyl-[ 1,2,4]oxadiazol-3-yl)-ethyl]-amine; Ethyl-[3-(4-methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-(3-methyl-[ 1,2,4]oxadiazol-5-ylmethyl)-amine; 3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-7-[2-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-piperidin-l-yl]-pyrazolo[l,5-a]pyrimidin. 4. A compound as claimed in claim 3, wherein the compound is selected from the group of: [3-(2,4-Dimethoxy-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[2,2,2-trifluoro-(S)-l-(3-methyl-[l,2,4]oxadiazol-5-ylmethyl)-ethyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine; [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine;and [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-l-methyl-2-(5-trifluoromethyl-[l,2,4]oxadiazol-3-yl)-ethyl]-amine. 5. A compound as claimed in claim 4, wherein the compound is selected from the group of: [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-1 -(3-methyl-[ 1,2,4]oxadiazol-5-yl)-propyl]-amine; and [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine. 6. A compound as claimed in claim 5, wherein the compound is [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(S)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine. 7. A compound as claimed in claim 5, wherein the compound is [3-(4-Methoxy-2-methyl-phenyl)-2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl]-[(R)-l-(3-methyl-[l,2,4]oxadiazol-5-yl)-propyl]-amine. 8. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier or diluent and a pharmaceutically effective amount as 0.1% to 99.9% of a compound as claimed in anyone from claim 1 to claim 7.

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