Title of Invention

NOVEL PROCESS FOR THE PREPARATION OF PYRAZOLOPYRIMIDINONES

Abstract

A proce'ss for the production of a compound of general formula I: wherein A represents CH or N; R1 represents linear C1-3 alkyl, which alkyl group is optionally interrupted by an oxygen atom, or is optionally terminated by a 2-pyridinyl group; R2 represents I(C1-4 alkyl; R3 represents alkyl, which alkyl group is optionally interrupted by an oxygen atom; R4 represents JC1.3 alkyl; 1 which proces^ comprises reaction of a piperazinylsulfonyl compound of formula II wherein Rx represents -NH2, -NHRa, -N(Rb)Rc", -SRd, -SH, -0Re (in which groups Ra to, Re each independently represent C1-3 alkyl, which alkyl group is optionally interrupted by an oxygen atom, or is optionally terminated by a 2-pyridinyl group or halo; with an amino: pyrazole carboxamide of general formula III wherein R1 and R2 are as defined above.

Full Text

FORM 2 THE PATENTS ACT 1970 [39 OF 1970] COMPLETE SPECIFICATION [See Section 10] "NOVEL PROCESS FOR THE PREPARATION of PYRAZOLOPYrilMIDINONES" PFIZER INC., ia corporation organised under the laws of the State of Delaware, United States of America.; of 235 East 42nd Street, New York, New York, 100il7, United States of America, The following specification particularly describes the nature of the invention and the manner in which it is to be performed:- This invention relates to a novel process for the production' of 4-al^lpiperazinylsulfonylphenyl- and 4-alkylpiperazinylsulfonyl pyriduiyl-dmydropysazolo[4,3-d]pyrimridin-7-one derivatives, and, in particular, the anti-ixnpotejnce drug, sildenafil and analogues thereof. li Sildenafil (i5- [2-ethoxy-5-(4-methylpiperazin-1 -ylsulfonyl)phenyl] -1 - ij metxiyl-3-ft[jpropyl-1,6-dihydro^ is the active ingredient in Viagra™. The compound, which was originally disclosed inj European patent application EP 463 756, has been found to be particularly luseful in the treatment of inter alia male erectile dysfunction (see international patent application WO 94/28902). ' Multi-step syntheses for the preparation of sildenafil are described in EP 463 756. Ah. improved process for its production is described in a later application jIEuropean patent application EP 812 845), the fmal step of which involves an internal cyclisation under basic, neutral or acidic conditions. We have now found that sildenafil and analogues thereof may be made via a novel process, as described hereinafter, which process has advantages over the processes described in the above-mentioned prior art documents. I: According jto a first aspect of the invention, there is provided a process for i the production of compounds of general formula I: wherein A represents CH or N; R1 represents H, lower alkyl (which alkyl group is optionally interrupted by O), Het, alkylHet, aryl or alkylaryl, which latter five groups are all optionally substituted (and/or, in the case of lower alkyl, optionally terminated); by one or more substituents selected from halo, cyano, nitro, lower alkyl, OR5, C(0)R6, C(0)OR7, C(0)NR8R9, NR10aR10b and S02NRllaRllb; R and R4 independently represent lower alkyl; R3 represents lower alkyl, which alkyl group is optionally interrupted by oxygen; Het represents an optionally substituted four- to twelve-membered heterocyclic group, which group contains one or more heteroatoms selected from nitrogen, oxygen and sulfur; R5, R6, R7,!R8, R9, Rlla and R1 lb independently represent H or lower alkyl; R10a and R(ob either independently represent, H or lower alkyl or, together with the nitrogen atom to which they are attached, represent azetidinyl, pyrollidinyl or piperidinyl, which process comprises the reaction of a compound of formula II, wherein R*is a group substitutable by an aminopyrazole and A, R3 and R4 are as defined above, 1 0 wherein R !and R are as defined above, with a compound of general formula DI, WO 01/98284 PCT/IB01/01050 which process is referred to hereinafter as "the process of the invention". The compcpunds of the general fonnulae I and III may be represented by either of the formulae I, IA and IB or IHA or IEDB in the process according to the present invention. ■MA IIIB The term '"aryl", when used herein, includes six- to ten-membered carbocyclici aromatic groups, such as phenyl and naphthyl and the like. Het groups: may be fully saturated, partly unsaturated, wholly aromatic, partly aromatic and/or bicyclic in character. Het groups that may be mentioned ; include groups such as optionally substituted azetidinyl, WO 01/98-284 PCT/IB01/01050 pyrrolidinyl, imidazolyl,., indolyl, oxadiazolyl, thiadiazolyl, triazoiyi, tetrazolyl,i oxatriazolyl, thiatriazolyl, pyridazinyl, morpholinyl, pyrrmidinyl, pyrazinyl,' pyridyl, quinolinyl, isoquinolinyl, piperidinyl, pyrazolyl, imidazopyridinyl, piperazinyl, thienyl and furanyl. The point of attachment of any Het group may be via any atom in the ring system including (where appropriate) a heteroatom. Het groups may also be present in the N- or ^-oxidised form. The term;"lower alkyl" (which includes the alkyl part of alkylHet and alkylaryl groups), when used herein, includes Q.6 alkyl (e.g. Cw alkyl). Unless otherwise specified, alkyl groups may, when there is a sufficient number ofjicarbon atoms, be linear or branched, be saturated or unsaturated, be cyclic, acyclic or part cyclic/acyclic, and/or be substituted by one or more halo atoms. As defined herein, the term "halo" includes fluoro, chloro, bromo and iodo. Compounds of formulae I, IA and IB may contain one or more asymmetric carbon atoms and may therefore exhibit optical and/or diastereoisomerism. The process of the invention thus also relates to the formation of stereoisomers of compounds of formulae I, IA and IB and mixtures thereof. Stereoisomers may be separated using conventional techniques, e.g. chromatography or fractional crystallisation. The various stereoisomers may be isolated by separation of a racemic or other mixture of the compounds using conventional, e.g. fractional crystallisation or HPLC, techniques. Alternatively the desired optical isomers may be made by reaction of the appropriate, optically active starting materials under conditions which will not cause racemisation or epimerisation, or by derivatisation, for example with a WO 01/98284' PCT/TB01/01050 homochiraL acid followed by separation of the diastereomeric esters by conventional means (e.g. HPLC, crystallisation, chromatography over silica or, for example, via classical resolution with a homochiral acid salt). The formation of all stereoisomers is included within the scope of the invention. Compounds' of formula H may exhibit tautomerism. The use of all tautomeric forms of the compounds of formula II is included within the scope of the invention. Preferred compounds of formulae I, IA and IB include those in which: R1 represents Cw alkyl, which alkyl group is optionally interrupted by an oxygen atom, and/or is optionally terminated by a. Het group (such as a pyridinyl group); R represents Ci^. alkyl; R represents Q.5 alkyl, which alkyl group is optionally interrupted by an oxygen atom; R represents Q.3 alkyl. More preferred compounds of formulae I, IA and IB include those in which: 1 R represents linear C1.3 alkyl, which alkyl group is optionally interrupted by an oxygen atom, or is optionally terminated by a 2-pyridinyl group (e.g. to form a 2-pyridinylmethyl group); t R represents linear C2-3 alkyl; R represents linear or branched C2-4 alkyl, which alkyl group is optionally interrupted by an oxygen atom; R represents Cy_2 alkyl. Particularly (preferred compounds that may be formed in the process of the invention include sildenafil, and the following four compounds: PCT/IBOl/01050 r 1C WO 01/98284 PCT/IBOl/01050 ID WO 01/98284 PCT/IB01/01050 Said compounds IB, 1C, ID and IE are otherwise known as: IB, (+)-3-ettryl-5- [5 jT d]pyrimidin-7-one also known as 3-Ethyl-5-{5-[4-ethylpiperazin-l-ylsulphonyl]-2-([(lR)-2-methoxy-l-methyleth}4]ox}0pyridin-3-yl}-2-methyl-2,6-dihydro-7H-pyrazolo[4,3-d] pyrimidin-7-one, the compound of Example. 118' of W099/54333; 1C, 3-ethyl-5-[5-(4-ethylpiperazin-l-ylsulphonyP-2-n-propoxyphenyl]-2-(pyridin-2-yl)methyl-2,6-dihydro-7H- p}Tazolo[4!J3-d]pyrimidin-7-one, the compound of Example 5 of W098/491J66; ID, 3-ethyl-5-[5-(4-ethylpiperazin-l-ylsulphonyl)-2-(2- methoxyemoxy)pyridm-3-yl]-2-(pyiidm-2-yl)methyl-2,6-dihydro-7H-. pyrazolo[4i3-d]pyrimidin-7-one, the compound of Example 4 of W099/543:33; and IE, 5-[2-Ethoxy-5-(4-ethylpiperazin-l- ylsulphonyl)pyridin-3-3d]-3-ethyl-2-[2-methoxyethyl]-2,6-dihydro-7H- pyrazolo[4;3-d]p3'rimidin-7-one, also known as l-{6-ethoxy-5-[3-ethyl-6,7-dmydro-2-(2-memoxyemyl)-7-oxo-2i7-p3Tazolo[4,3-^pyrhTndin-5-yl]-3-pyrid3'l sulphonyl }-4-ethylpiperazine, the compound of Example 8 of IB00/01457, exemplified hereinafter as Example 3. 20 By "group subsritutable by an aminopyrazole having structure in" we include any group which, when present in the moiety -C(RX)=NH of a compound of formula II, may undergo displacement by the amino group of 25 an arninop3>razole such that a -C(=NH)-NH- linkage is thereby formed. In accordance with the process of the invention, which the skilled person will appreciate involves a "one-pot" condensation/cyclisation reaction, the aminopyrazole that is reacted with the compound of formula II is a compound of formula HI, HIA or lllH. Following the condensation WO '01/98284 PCT/IB01/01050 reaction, the coupled intermediate undergoes cyclisation to form a compound ojf general formula I. In this respect, preferred groups that Rx may represent include -NH2, -NHRa, -N(Rb)Rc, -SRd, -SH, -ORe wherein groups Rb to Rc each independentJjy represent the same groups that R as hereinbefore defined may represent (except that they do not represent H or alkoxy) as well as halo (e.g. chloro). Group Ra represents -OR1 or halo (e.g. chloro) wherein R1 is as hereinbefore defined. More preferred values of Rx include -NHRa, -N(Rb)Rc, and preferably -SRd, -SH and -ORc. Particularly preferred values of Rx are Cd alkoxy (e.g. ethoxy). i' !: '■ • According tcj a firrther aspect of the invention, there is provided a process for the production of a compound of formula I, IA or IB, as hereinbefore defined, which process comprises the reaction of a compound of formula HI, IUA or IIIH I (as appropriate), as hereinbefore defined, with a compound of j! formula n, as hereinbefore defined, provided that Rx does not represent -NH2, or, preferably, Rx does not represent -NH2, -NHRa or -N(Rb)Rc. The process of the invention may be carried out in the presence of a suitable organic solvent system, which solvent system should not significantly react chemically with, or significantly give rise to stereochemical changes in, the reactants or product once formed, or significantly give rise to other side i, reactions. Preferred solvent systems include aromatic hydrocarbons (e.g. toluene or xylene) or chlorobenzene. Preferred solvent systems also include solvents of formula RXH, for example, solvents of formula RcOH (e.g. ethanol), wherein Rx and Rc are as hereinbefore defined. WO 01/98284 PCT7IB01/01050 In the process of the invention, it may be preferable to add compounds of formulae iin, IHA or IUB to die reaction mixture (prior to carrying out the reaction) in a suitable polar organic solvent such, as ethyl acetate. Such a polar solvent may then be removed before the reaction is initiated. Hie process of the invention may be carried at elevated temperature (e.g. up to the reflux temperature of the relevant solvent system, or higher if a pressurised system is employed). Clearly, appropriate reaction times and reaction temperatures depend upon the solvent system that is employed, as well as the reactants that are used and the compound that is to be formed, but these may be determined routinely by the skilled person. We have; found that compounds of formula II may be prepared, advantageously, by way of reaction of a compound of formula IV, IV wherein G represents a carboxylic acid group (-C(O)OH) or a derivative thereof, and A, R and R are as hereinbefore defined, with an appropriate reagent for converting the group G to a -C(RX)=NH group, wherein Rx is as hereinbefore defined. The term "derivative of a carboxylic acid group" when used herein includes groups which are commonly derived from a carboxylic acid and/or groups WO 01/98284 PCT/IB01/01050 that contain a central carbon atom (which carbon atom is attached to the phenyl or pyridyl ring in the compound of formula IV) that is at the same oxidation state as -C(0)OH. The term therefore includes groups such as -CN, -C(ORJ*)3, -C(0)NH2 or -C(=NORf)N(Re)2, wherein Rf represents H or lower alkyhand Re is as hereinbefore defined. G can also represent a 5- or 6-memebered heterocyclic group containing at least two heteioatoms selected from 0, S, N and mixtures thereof wherein said heterocyclic group is bonded bjy a carbon atom, a preferred heterocyclic group, as exemphfied in preparation 4 herein, has the general formula -C(=NORs)N(Re) wherein the carbon is bonded to both N atoms and wherein Rg is bonded to the N of i the -NRe group and wherein Rs is a -CH, or a -CH2- group and wherein Re Is as defined hereinbefore and is: preferably H or lower alkyl or lower ilkoxy. ' : ' Preferred compounds of formula IV include those in which, when A •epresents GH, then G does not represent -C(0)OH. Procedures for the conversion of selected groups which G may represent to :ertain -C(RX)=NH groups are known to those skilled in the art, and are lescribed inter alia in: J. March, Advanced Organic Chemistry, 3rd Edition, :hapter 10j! 371-374, John Wiley & Sons (1985); and Comprehensive Organic Functional Group Transformations, edited by A. Katritzky, O. 4eth-Cohn,:!and C. Rees, 1st Edition, Volume 5, Sections 5.17 (page 653) nd 5.19 (page 741), Pergamon Press (1995), the disclosures of which locuments are hereby incorporated by reference. For example, compounds •f formula II may be prepared by way of the following procedures. WO 01/98284 PCT/IB01/01050 1) For compounds of formula II in which Rx represents -ORe (wherein Re represents lower alkyl (optionally interrupted by 0), alkylHet or alkylaryl, e.g. lower alkyl): (a) a corresponding compound of formula IV in which G represents - CN may be reacted with an alcohol of formula VA, RaOH VA wherein Ra represents lower alkyl (optionally inteirupted by O), alkylHet or alkylaryl (e.g. lower alkyl), and Het is as hereinbefore i, defined, in the presence of a suitable protic acid (e.g. HC1 gas) and optionally in the presence of an appropriate solvent (e.g. diethyl ether, dioxan, benzene or chloroform). The skilled person will appreciate that such a reaction may be performed at low ■ij . ■ ■■ ' . temperature (e.g. below 5°C); I . . )) ai corresponding compound of formula IV in which G represents -G'(0)NH2 may be reacted with an appropriate alkylating agent of formula VB, RcrZ1 VB • wherein Z1 represents a leaving group such as halo, -OS(0)2ORa, -OS(0)2CF3 or ORa2, and Ra is as hereinbefore defined, optionally in the presence of a suitable solvent (e.g. dichloromethane), followed by deprotonation of the resulting alkoxymemyleneirninium salt in the presence of a suitable base (e.g. NaOH or a tertiary amine such as triemylamine); or ) a corresponding compound of formula IV in which G represents -C(ORa)3, wherein Ra is as hereinbefore defined, may be reacted with ammonia, or an /V-protected derivative thereof, for example in the presence of a catalytic quantity of a suitable acid (e.g. a WO 01/98284 PCT/IB01/01050 protic acid such as p-toluenesulfonic acid), and optionally in the presence of an appropriate solvent (e.g. dichloromethane). ) For compounds of formula II in which Rx represents -ORe (wherein Re i represents Het or aryl, e.g. phenyl), a corresponding compound of formula IV in which G represents -CN may be reacted with a compound of formula VC, RpOH VC wherein Rp represents Het or aryl (e.g. phenyl), and Het is as hereinbefore defined, for example in the presence of a suitable catalyst (e.g. a; Lewis acid such as ZnCl2 and/or a protic acid such as HC1) and optionlally in the presence of an appropriate solvent (e.g. dichloromethane). . i' . I For compounds of formula II in which Rx represents -NH2: i; (a) ai corresponding compound of formula IV in which G represents - GN may be reacted with hydrazine, hyolroxylamine or (b) ai corresponding compound of formula IV in which G represents - G(=NORf)N(Re)2, wherein Rf is as hereinbefore defined, may be reduced under standard conditions (e.g. palladium-catalysed Hydrogenation). For compounds of formula II in which Rx represents -NH2; -NHRa or -N(R )RC, a corresponding compound of formula IV in which G represents -CN may be reacted with a compound of formula VD, WO 01/98284 PCT/EB01/01050 HN(RX)(R6) VD wherein Rx and Rs independently represent H or Ra, and Ra is as hereinbefore defined, for example in the presence of a suitable catalyst (e.g. a copper(I) salt such as CuCl) and optionally in the presence of an appropriate solvent (e.g. dhnethylsulfoxide or a lower alkyl alcohol such &s methanol or ethanol). ) For compounds of formula II in which Rx represents -SH: (a) a corresponding compound of formula IV in which G represents -CN may be reacted with hydrogen sulfide, for example in the presence of a suitable base (e.g. a tertiary amine such as tnethylamine) and optionally in the presence of an appropriate Solvent (e.g. a lower alkyl alcohol such as ethanol); or (b) a corresponding compound of formula IV in which G represents -C(0)NH2 may be reacted.with a reagent that effects oxygen-sulfur exchange (e.g. P4S10 or Lawesson's reagent), for example, in the presence of an appropriate solvent (e.g. toluene). For compounds of formula II in which Rx represents -SRd, a corresponding compound of formula IV in which G represents -CN may bie reacted with a compound of formula VE, RdSH VE wherein Rd is as hereinbefore defined, for example in the presence of a suitable base (e.g. a tertiary amine such as triemylamine) and optionally in the presence of an appropriate solvent (e.g. a lower alkyl alcohol such as ethanol). For compounds of formula II in which Rx represents halo (e.g. chloro), a corresponding compound of formula IV in which G represents - "WO 01/98284 PCT/IB01/01050 C(0)NH2 may be reacted with a suitable halogenating agent (e.g. a chlorinating agent such as PC15 or S(0)C12), optionally in the presence of ah appropriate solvent (e.g. benzene, CC14, CHC13 or dichloromethane). Compounds of formula II may similarly be prepared from other compounds of formula I'll by reaction with a reagent that will convert one Rx group to another. In this respect, compounds of formula II may additionally be 1 prepared by way of the following procedures. For compounds of formula II in which Rx represents ORe (wherein Re represents lower aiiyl, alkylHet or alkylaryl, e.g. lower alkyl), a corresponding compound of formula II in which Rx represents CI may 1: be reacted with a compound of formula VA, as hereinbefore defined, for example in the presence of an appropriate solvent (e.g. dichloromethane) and a suitable base (e.g. an alkali metal alkoxide such a's sodium ethoxide, or a tertiary amine such as triemylamine). For compounds of formula II in which Rx represents -NH2, -NHRa or -N(Rb)Rc, a corresponding compound of formula II in which Rx represents CI, -SH, -SRd or -ORe, wherein Rd and Rc are as r hereinbefore defined, may be reacted with an appropriate compound of I, formula VD, as hereinbefore defined, or an acid (e.g. hydrogen chloride or CH3C(0)OH) addition salt thereof, for example optionally in the' presence of an appropriate solvent (e.g. dichloromethane, ethanol, diethyl ether, dioxan, benzene or chloroform) and/or a suitable reaction promoter (for example: for reaction of compounds of formula II in which Rx represents -SH, a mercury(H) salt to act as a sulfide scavenger; and for reaction of compounds of formula II in which Rx represents -SRd, a pH buffer (e.g. sodium acetate / acetic acid)). HI) For compounds of formula II in which Rx represents -SRd, a corresponding compound of formula II in which Rx represents -SH may be reacted with a compound of formula VF, Rd-Z2 VF wherein Z2 represents a leaving group such as halo (e.g. iodo), alkanesulfonate, perfluoroalkanesulfonate (e.g. trifluoromethane-sulfonate) or arenesulfonate (e.g. p-toluenesulfonate), and Rd is as hereinbefore defined, optionally in the presence of an appropriate . solvent (e.g. dichloromethane or acetone) and/or a suitable base (e.g. a . tertiary amine such as triethylamrne). Compounds; of formula IV may be prepared via a variety of techniques. For example: (a) Compounds of formula IV may be prepared by reaction of a compound of formula VI, VI L' wherein L1 is a leaving group (e.g. halo) and A, G and R3 are as hereinbefore defined, with a compound of formula VU, R-N\|H VII V_7 wherein R4 is as hereinbefore defined. This reaction' may be performed at, for example, low temperatures (e.g. between -10°C and room, temperature), in the presence of an appropriate solvent (e.g. a Q. 3 alcohol, ethyl acetate, dichloromethane, toluene or heptane), at least one [equivalent of the compound of formula VR and, optionally, • anotrier suitable base (such as a base that does not react with or, if it does [react, a base that further activates the sulfonyl chloride (for i, example: a tertiary amine such as triethylamine, N- i ethyljdmopropylamirie, l,5-diazabicyclo[4.3.0]non-5-ene or 1,8- diazabicyclo[5.4.0]undec-7-ene; or a metal hydride, oxide, carbonate or bicarbonate)). Compounds of formula VI are available using known techniques. For example, compounds of formula VI may be prepared from a ii ■ ■ corresponding compound of formula Vm, OR3 'G VII! wherein A, G and R are as hereinbefore defined, for example using conventional methods for the introduction of a -SO2L1 group into an aromatic or heteroaromatic ring system, such as reaction of a compjound of formula "VTH, optionally in the presence of an appropriate solvent (e.g. dichloromethane), with a compound of ' 1 i formula L S03H and (optionally) a compound of formula SO(L )2. When L1 is chloro, reaction may take place at between 0°C and room temperature in the presence of an excess of chlorosulfonic acid (optidnally in conjunction with an excess of .thionyl chloride), and optionally in an appropriate organic solvent (e.g. dichloromethane). (b) Compounds of formula IV in which G represents -CN or -C(0)NH2 may be prepared by reaction of a compound of formula IX, 2 wherein Q represents -CN or -C(0)NH2, L represents a suitable leaving group and A and R4 are as hereinbefore defined, for example by reaction with a compound that will provide the group R O (e.g. an !' '• • • alkoxide base). This route is preferred for the preparation of compounds of formula IV in which A represents N. Suitable leaving groups L2 include standard groups known to those skilled in the art, such as optionally substituted arylsulfonyloxy groups (e.g. ;p-toluenesulfonyloxy), optionally substituted d_4 alkane-sulfonyloxy groups (e.g. methanesulfonyloxy, trifluoromethane-sulforjyloxy), halosulfonyloxy (e.g. fluorosulfonjdoxy), halonium, diarylsulfonylamino (e.g. ditosyl), quaternary ammonium C^ alkyl-sulfonyloxy, Cw perfluoroalkanoyloxy (e.g. trifluoroacet5'-loxy), CM alkanoyloxy (e.g. acetyloxy), aroyloxy (e.g. benzoyloxy), diazonium, oxonium or perchloryloxy groups. More preferred values of L2 include a different lower alkoxy group to that which is to be replaced by the group R O (e.g. methoxy, provided that R3 does not represent methyl) and, especially, halo (including bromo and, particularly, chloro). The sjkilled person will appreciate that compounds that may serve to 3 provide the group R O include lower alkoxides of alkali metals (e.g. hthium, sodium, potassium), or of alkaline earth metals (e.g. magnesium, calcium). Preferred alkoxides mclude those of sodium and potassium. Alternatively,, the R 0" anion may be produced in situ by reaction of the relevant lower alkyl alcohol (or an alkali/alkaline earth metal ■ alkoxicie) with an auxiliary base, which should not compete with the relevant R3(X group in the nucleophilic substitution of L2 by being suitably sterically hindered. In this respect, suitable auxiliary bases may include a sterically hindered alkoxide or a secondary or tertiary amine!1 Compounds of formula IX may be prepared by reaction of a compound of formula X, wherein A, Q and L/ are as hereinbefore defined with a compound of formula VH as hereinbefore defined, for example as described hereinbefore. Compounds of formula X may be prepared by known techniques. For example compounds of formula X in which both L2 groups represent halo (e.g. chloro) may be prepared by reaction of a corresponding compound of formula XI, . wherein A and Q are as hereinbefore defined, with a suitable halogenating agent (e.g. thionyl chloride), for example at around 80 to 100°G| optionally in. the presence of a suitable solvent (e.g. ij djrnethylformamide) and/or (optionally) an appropriate activating agent !(e.g. dimethylformamide). The skilled person will appreciate that when an activating agent and a solvent are both employed, they may bje either the same or different compounds. Compounds of formula XI may be prepared by techniques known to those Skilled in the art. For example, compounds of formula XI may be prepared by reacting a corresponding compound of formula XII, wherein A and Q are as hereinbefore defined, with a sulfonating agent (e.g. oleum) under conditions known to those skilled in the art. Compounds of formula TV in which G represents -CN may alternatively be prepared by dehydration of a corresponding compound of formula IV in which G represents -C(0)NH2, under appropriate reaction conditions, for example at low temperature (e.g. at between -5°C and room temperature (preferably at around 0°C)) in the presence of a suitable dehydrating agent (for example: P205; POCl3; PC15; CC14 and triphenylphosphine; trifluoroacetic anhydride and a suitable base (e.g.itriemylamine or pyridine); or SOCl2) and an appropriate organic solvent (e.g. dichloromethane, toluene, chlorobenzene or heptane). (d) Compounds of formula IV in which G represents -C(0)NH2 may be prepared from a corresponding compound of formula IV in which G represents -C(0)OH, for example by reaction with ammonia or a . derivative thereof (e.g. ammonium acetate). The skilled person will appreciate that this reaction may preferably be carried out in the presence of an appropriate activating reagent (e.g. NJF-'..: carbonyldiimidazole), in an appropriate solvent, e.g. ethyl acetate, dichldromethane or butan-2-one, resulting in the formation of an . intermediate imidazolide (which may be isolated if desired), followed i' . ' ■ by reaction with e.g. ammonium acetate at between room and reflux i temperature. Those skilled in the art will also appreciate that the activation of benzoic acid derivatives may also be accomplished with many; other activating agents, for example as described in J. March, Advanced Organic Chemistry, 3r Edition, Chapter 10, 371-374, John Wiley & Sons (1985). (e) Compounds of formula IV in which G represents -C(0)OH may be prepared by known techniques. For example, such compounds may be prepared according to, or by analogy with, methods described in European patent application EP 812 845 (the disclosures in which document are hereby incorporated by reference). Compounds of formula IV in which G represents -C(0)OH may alternatively be prepared by reaction of a corresponding compound of formula XUJ, >V0 01/98284 PCT/IB01/01050 wherein A and L2 are as hereinbefore defmed, with a compound that with provide the group RJ0, for example under conditions as described hereinbefore for the preparation of compounds of formula IV. Compjounds of formula XHI may be prepared by known techniques, for example, according to, or by analogy with procedures described hereinbefore for the preparation of compounds of formula EX. i Other compounds of formula IV may be prepared from appropriate starting I; materials (which include inter alia compounds of formula IV), using techniques I known to those skilled in the art and/or according to, or by analogy, with procedures described hereinbefore for the preparation of compounds !of formula II. Compounds! of formulaULA, IHB, VA, VB, VC, VD, VE, VF, VH, Vm, XII, and dbrivatives thereof, when not commercially available or not subsequently described, may be obtained either by analogy with processes described herein, or by conventional synthetic procedures, in accordance with standard techniques, from readily available starting materials using i' appropriate reagents and reaction conditions. Compounds' may be isolated from reaction mixtures using known techniques. Substituents i on the aryl (e.g. phenyl), and (if appropriate) heterocyclic, group(s) in compounds defined herein may be converted to other substituents using techniques well known to those skilled in the art. For example, amino may be converted to amido, amido may be hydrolysed to amino, hydroxy may be converted! to alkoxy, alkoxy may be hydrolysed to hydroxy etc. WO 01/98284 PCT/IB01/01050 It will be appreciated by those skilled in the art that, in the processes described above, the'functional groups of intermediate compounds may be, or may need to be, protected by protecting groups. Functionali groups which it is desirable to protect thus include hydroxy, amino I; and caiboijcylic acid. Suitable protecting groups for hydroxy include trialkylsilyii and diarylalkylsilyl groups (e.g. te7?-butyldimethylsilyl, tert- i butyldipheriylsilyl or . trimethylsilyl), tetrahydropyranyl, benzyl . and alkylcarbonyl groups (e.g. methyl- and ethylcarbonyl groups). Suitable protecting |jgroups for amino include benzyl, ferf-butyloxycarbonyl, 9- fluorenylmethoxycarbonyl.or benzyloxycarbonyl. Suitable protecting groups for carboxyiic acid include Q.6 alkyl, allyl or benzyl esters. - ■ i; . ' • I; The protection and deprotection of functional groups may take place before or \ after any of j'the reaction steps described hereinbefore. Protecting groups may be removed in accordance with techniques which are . |l well known! ito those skilled in the art and as described hereinafter. The use of j protecting groups is fully described in "Protective Groups in Organic Chemistry", edited by JWF McOmie, Plenum Press (1973), and "Protective jGroups in Organic Synthesis", 3rd edition, TW Greene & PGM Wutz, Wileyj-Interscience (1999). 11 Persons skilled in the art will appreciate that, in order to obtain compounds of the formula{H in an alternative, and, on some occasions, more convenient, manner, the 'individual process steps mentioned herein may be performed in a different ordier, and/or the individual reactions may be performed at a different WO 01/98284 PCT/IB01/01050 stage in the overall route (i.e. substituents may be added to and/or chemical transformations performed upon, different intermediates to those associated |.| hereinbefore with a particular reaction). This will depend inter alia on |l factors such as the nature of other functional groups present in a particular |i substrate, the availability of key intermediates and the protecting group strategy (if 'any) to be adopted. Clearly, the type of chemistry involved will influence the choice of reagent that is used in the said synthetic steps, the need, and type, of protecting groups that are employed, and the sequence for l| accomplishing the synthesis. Certain intermediates that are employed in the processes described herein are...novel. According to the invention there is further provided: (a) compounds of formulae II as defined hereinbefore; and (b) compounds of formula TV as defined hereinbefore. Preferred compounds of formula II include those in which, when A represents CH, then R does not represent -NH2. According to a further aspect of the invention there is provided compounds of formula H, as defined hereinbefore, in which Rx represents -SRd, -SH and -ORe (wherein Rd and Rc are as hereinbefore defined). The process1 of the invention may have the advantage that sildenafil and analogues thereof may be prepared from commercially-available starting materials in fewer steps than in processes described in the prior art, without concomitant- losses in terms of yield of key intermediates and of final products. WO 01/98284 PCT7DB01/01050 Further, the process of the invention may have the advantage that sildenafil and analogues thereof may be prepared in less time, more conveniently, and at a lower cbst, than when prepared in processes described in the prior art. j' The invention is illustrated, but in no way limited, by the following examples. All H NMIjt spectra were recorded using a Varian Unity 300 MHz machine. Example 1 5-[2-Embxy-5-(4-memvlpiperazin-l-vlsulfonvl)phenvl1-l-methvl-3-ra- propyl4,6-dmvdro-7J7-pwa2olor43-dlpyrirrudiii-7-one, sildenafil ■ ii '■ r^~- : . 0 A solution of . ethyl 2-ethoxy-5-(4-methyl-l-piperazinylsulfonyl)-benzimidate, (2.2 g, 6.2 rnmol, from step 1(c) below) and 4-amino-l-methyl-3-propyl-liI-pyrazole-5-carboxamide (Example 37 of EP 0463756) (17 mL of a 10% w/v solution in ethyl acetate, 6.8 rnmol) in xylene (40 mL) was heated to reflux. Approximately 10 mL of the solvent was distilled to remove the ethyl acetate. The reaction started to foam at 129°C and gave off ammonia gas. The temperature gradually rose to 136°C over three days WO 01/98284 PCT/IBO1/01050 and the foaming ceased. When the reaction was complete, the solvent was i' removed to: give a brown oil which was further purified using medium j! pressure column chromatography (DCM and methanol as eluents), giving the title product in 76% yield, along with recovered 4-amino-l-methyl-3- propyl-lH-pyrazole-5-carboxamine (22.6%). The yield based upon unrecovered 4-amino-1 -meflryl-3-propyl- lijr-pyrazole-5-carboxamide was 85%. The product was recrystallised from metlryl ethyl ketone (MEK) to give material for analysis. mp 184-185;°C JH NMR (GDC13) 8 1.03 (3H, t), 1.62 (3H, t), 1.85 (2H, m), 2.22 (3H, s), .2.49 (4H, m), 2.94 (2H, t), 3.11 (4H, m);-4.27 (3H, s), 4.38 (2H, q), 7.17 (m,d), 7.83 (1H, d), 8.81 (1H, s) m/z found 475 [M+H]+ 100%, C22H3iN604S requires 475 Preparative Examples for Example 1 1 (a) 5-Chloibsulfonvl-2-ethoxvbenzonitrile! (Compoundlof formula VI where A=CH; R3=Et; G=CN; L=C1) Commercially available 2-ethoxybenzonitrile (1.0 g, 0.007 mol) was added to an ice-cold solution of chlorosulfonic acid (1.9 mL, 0.03 mol) and thionyl chloride (0'.|5 mL, 0.007 mol) over 30 minutes, left to stir overnight, quenched by pouring onto ice/water (20 mL), and granulated for 30 minutes. The precipitated product was filtered off, washed with water and dried on the filter under nitrogen to give 1.0 g (59%) of the sub-title compound as a yellow solid, which was used directly in the next step. ]H NMR (CDCI3) 5 1.54 (3H, t), 4.31 (2H, m), 7.16 (1H, d), 8.18 (1H, d), 8.12 (1H, s) WO 01/98284 PCT/IB01/01050 1 (b) 2-Etho'^v-5-f4-methvl-l-pipera2inylsulfonvl)benzonitrile (compound bf formula IV where A=CH: R3=Et; G=CN: R4=Me) 5-CMorosullfon3d-2-ethoxybenzonitrile (1.0 g, 0.004 mol, from step 1(a) above) was' dissolved in dichloromethane (DCM; 6 mL) and cooled to I; between 0 and 5°C. N-Methylpiperazme (0.8 mL, 0.0091 mol) was added dropwise oyer 30 minutes and the solution left to stir overnight The solution was diluted with 10 mL of water and the product extracted with dichloromethane. The solvent was removed in vacuo to give the sub-title compound as a yellow oil (0.8 g, 66.6%). ]H NMR(GjDCl3) 5 1.54 (3H, t), 2.2 (3H, s), 2.45 (4H, m), 2.97 (4H, m), 4.18 (2H, qj[ 7.07 (1H, d), 7.84 (1H, d), 7.90(1H, s) 'i m/z found 3*10 [M+H4] 75%, C14H19N3O3S requires 310 1(c) Ethyl 2Jlethoxv-5-(4-methvl-l-piperazinvlsulfonvl)benzrmidate * (compound of formula II where A=CH; R =Et; R =Me) A suspensi&n of 2-ethoxy-5-(4-metbyl-l-piperazmylsulfonyl)benzonitrile (2.6 g, 8.4 mmol, from step 1(b) above) in ethanol (80 mL) was cooled to 0° C. HCl gas !was slowly bubbled through the resultant until saturation. After standing forji3 days, the reaction was complete and ethanol was removed in vacuo. TheJ!crude solid was dissolved in DCM and washed with aqueous sodium bicarbonate solution. The solvent was removed to give the sub-title compound as a brown solid (48%). mp 158-160?C WO 01/98284 PCT/IB01/01050 ]H NMR (0DC13) 5 1.39 (3H, t), 1.56 (3H, t), 2.53 (3H, s), 2.S9 (4H, m), 3.32 (4H, m), 4.14 (2H, q), 4.37 (2H, q), 7.08 (1H, d), 7.74 (1H, d), 8.15 (1H.S) j; m/z found 3J57 [M+H]+ 25%, C16H26N304S requires 357 lfd) Alternative Synthesis of 2-Ethoxv-5-C4-methvl-l-piperazuivlsulfonyl)- benzonitrile! - the compound of Step 1(h) above 1 (d)(i) 2-Ethoxy-5-(4-methyl-1 -piperazinylsulfonvDbenzamide (compoundlof formula n where A=CH; R=Et; G=C(0)NH9; R=Me) • To a slurry of 2-ethoxy-5-(4-methyl-l -piperazinylsulfonyl)benzoic acid (50 g, 0.15 imoL see EP 812 845) in EtOAc (250 mL), was added NJT- carbonyldiirpidazole (CDI; 27 g, 0.166 mol) in one portion. The slurry was heated to arJout 40°C, upon which the reaction commenced. After the CDI had reacted) the reaction was heated to reflux, for 4 hours. Ammonium acetate (40 g, 0.5 mol) was added to the slurry, and the resultant was left to reflux overnight. After cooling the resultant slurry was filtered to give the sub-title product as a fine white solid (40.7 g, 83%). mpl85-189jPC !H NMR (GDC13) 8 1.58 (3H, t), 2.29 (3H, s), 2.47 (4H, m), 3.06 (4H, m), 4.29 (2H, q), 6.13 (1H, s), 7.12 (1H, d), 7.70 (1H, s), 7.82 (1H, d), 8.60 (1H, s) m/z found 328 [M+H4] 100%, Q4H22N3O4S requires 328 1 (d)Cii) 2-Ethoxy-5-(4-methvl-1 -piperazinylsulfonvDbenzonitrile (compound of formula II where A=CH; R3=Et; G= CN; R4=Me) WO 01/98284 PCT7IB01/01050 To an ice cold suspension of 2-ethoxy-5-(4-methyl-l-piperazinyl-shlfonyl)be'rizamide (32 g, 0.098 mol, from step 1(d)(1) above) and triemylamine (56 mL, 0.38 mol) in DCM was added trifluoroacetic li anhydride (34.4 mL, 0.22 .mol) which resulted in a brown solution. This was allowed to stir overnight and was quenched with water (100 mL). The organic layer was washed with water (2 x 100 mL) and brine (50 mL) and j] the DCM was removed in vacuo to give 56.8 g of brown oil which was !i recrystalhsed from ethyl acetate to give the product as a brown solid (18.7 g, 61.7%). r mp 119-120°C .... H NMR (GDCI3) 5 1.54 (3H, t), 2.2 (3H, s), 2.45 (4H, m), 2.97 (4H, m), 4.18 (2H, q)| 7.07 (1H, d), 7.84 (1H, d), 7.90QH, s) m/z found 310 [M+lT] 75%, C14Hi9N303S requires 310 ■ i I; •■ . The product jof Preparative example 1(d) may be used to prepare compounds of formula II, and of formula I, in which R is ethyl and. R is methyl, by employing similar procedures to those described in Example 1, and in the :! preparative Example step 1(c). Example 2 Alternative Synthesis of (5-r2-ethoxv-5-f4-methylpiperazin-l- ylsulfonvDphenyll-1 -methyl-3-n-propyl-1,6-dihvdro-7ff-pyrazolo f4.3- dlpyrimidin-7-one). Sildenafil. WO 01/98284 PCMB01/01050 4-Amino-1 -methyl-3-72-propyl-liir-pyra2ole-5-cafboxylate (prepared according to Example 37 of EP-0463756) (0.182 g, 1.0 mMol) and 2-emoxy-5-(4^me(iyl-l-piperazmylsulfonyl)benzan^dine (the compound of Preparati.onji5 hereinafter) (0.326 g, 1.0 mMol) were stirred in xylene (15 r - ■ mL) and this mixture was heated to reflux for 9h. After evaporation and re- i evaporation!1 from toluene the residue was subjected to chromatography on silica gel eliiting with ethyl acetate / methanol mixtures to give the desired product, 0.033g. M/Z = 475 (M+H); 1H NMR (300MHz, CDC13); 1.04 (t, 3H), 1.66 (i 3H), 1.88 (sextet, 2H), 2.29 (s, 3H), 2.51 (m, 4H), 2.95 (t, 3H), 3.13 (m, 4H), 4.29 (s, 3H), 4.39 (quart. 2H), 7.16 (d, 1H), 7.85 (dd; 1H), 8.85 (d,lH): According to a preferred process according to the present invention there is provided a process for the preparation of sildenafil substantially as described in Examples 1 and 2 herein before and Preparations for Example 1 herein before. According to another preferred process compounds wherein G=C02Et can be prepared via the telescoped chemistry of Preparation 2 as detailed hereinafter. WO 01/98284 PCT7EB01/01050 Example 3: illustrates how one of the preferred compounds noted herein can be made. ' The present invention provides an alternative method for the preparation of the compound of Example 3 by using an)7 of the routes hereinbefore detailed and especially as described in Examples 1 and 2. I Example 3 2-(Methoxyemvl)-5-r2-emoxv-5-(4-emylpiperazm-l-vlsulphonvl)pvridin-3- !■ yl]-3-ethvU'2,6-dmydro-7H-pvrazolor4,3-d1pvrmiidm-7-one A mixture \ of the product from step 3(j) below (0.75mmol), potassium. bis(1rimethylsilyl)amide (298mg, 1.50mmol) and ethyl acetate (73 microlitres, l0.75mmol) in ethanol (10ml) was heated at 120°C in a sealed vessel for 12 hours. The cooled mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate solution, and the layers separated. The organic phase was dried (MgS04), and evaporated under reduced pressure. Tlie crude product was purified by column chromatography on silica gel using dichloromethane:methanol (98:2) as eluant to afford the title compound, 164mg; Found : C, 53.18; H, 6.48; N, 18.14; C23H33N7O5|S;0.20C2H5CO2CH3 requires C, 53.21; H, 6.49; N, 18.25%; 8 (CDC13) : 1.04 (3H, t), 1.40 (3H, t), 1.58 (3H, t), 2.41 (2H, q), 2.57 (4H, m), 3.08 (2H, q), 3.14 (4H, m), 3.30 (3H, s), 3.92 (2H, t), 4.46 (2H, t), 4.75 (2H, WO 01/98284 PCTVIBOI/OIOSO q), 8.62 (lfi, d), 9.04 (1H, d), 10.61 (1H, s); LRMS : m/z 520 (M+l)+; mp 161-162°C, Preparation!of Starting Materials for Example 3 ii 3(a) Pyridme-2-airrino-5-sulphonic acid 2-Aminopyridine (80g, 0.85mol) was added portionwise over 30 minutes to oleum (320g) and the resulting solution heated at 140°C for 4 hours. On cooling, thejreaction was poured onto.ice (200g) and me mixture stirred in an ice/salt bath for a further 2 hours. The resulting suspension was filtered, the sohd wajshed with ice water (200ml) and cold IMS (200ml) and dried under suction to afford the sub-tide compound as a sohd, 111.3g; LRMS : m/z 175 (Mf 1)+. 3(b) Pyridine-2-aTnino-3-bromo-5-sulphoiiic acid. 1 Bromine (9Sjg, 0.62mol) was added drop wise over an hour, to a hot solution of the product from step 3(a) (108g, 0.62mol) in water (600ml) so as to maintain a steady reflux. Once the addition was complete the reaction was cooled and the resulting mixture filtered. The solid was washed with water and dried under suction to afford the sub-title compound, 53.4g; 5 (DMSOd6,3t)0MHz): 8.08 (1H, s), 8.14 (1H, s); LRMS : m/z 253 (M)+. WO 01/98284 . PCT/IB01/01050 3(c) Pyiidine-3-bromo-2-chloro-5-sulphonvl chloride A solution of sodium nitrite (7.6g, llQ.Ommol) in water (30ml) was added !i dropwise toll an ice-cooled solution of the product from step 3(b) (25.3g, lOO.Ommol) in aqueous hydrochloric acid (115ml, 20%), so as to maintain the temperature below 6°C. The reaction was stirred for 30 minutes at 0°C and for a further hour at room temperature. The reaction mixture was evaporated under reduced pressure and the residue dried under vacuum at 70°C for 72.hours. A mixture of this solid, phosphorus pentachloride (30.0g, 144mmol) and phosphorus oxychloride (1ml, 10.8mmol) was heated at 125°C for 3 ihours, and then cooled. The reaction mixture was poured onto ice (lOOg) and the resulting solid filtered, and washed with water. The product was||dissolved in dichloromethane, dried (MgSC>4), and evaporated i under reduced pressure to afford the sub-title compound as a yellow solid, 'i 26.58g; 6 (cbci3, 300MHz): 8.46 (1H, s), 8.92 (1H, s). 3 (d) 3-Broiho-2-chloro-5-(4-ethylpiperazin-1 - vlsurphonvDp vridine A solution of 1-ethylpiperazine (11.3ml, 89.0mmol) and triemylamine (12.5ml, 89.pmm.ol) in dichloromethane (150ml) was added dropwise to an WO01/98284 PCT/IB01/01050 ice-cooled solution of the product from step 3(c) (23.Og, 79.0mmol) in dichloromethane (150ml) and the reaction stirred at 0°C for an hour. The reaction mixture was concentrated under reduced pressure and the residual -brown oil jwas purified by column chromatography on silica gel, using an elution gradient of dichloromethane:methanol (99:1 to 97:3) to afford the sub-title compound as an orange solid, 14.5g; 5 (CDC13| 300MHz) : 1.05 (3H, t), 2.42 (2H, q), 2.55 (4H, m), 3.12 (4H, m), 8.24 (1H, s), 8.67 (1H, s). 3(e) 3-Brbmo-2-ethoxv-5-(4-ethvlpiperazin-1 -vlsulphonvDpvridine A mixture 'of the product from stage 3(d) (6.60g, 17.9mmol) and sodium ethoxide (6:09g, 89.55mmol) in ethanol (100ml) was heated under reflux for 18 hours, then cooled. The reaction mixture was concentrated under reduced pressure, the residue partitioned between water (100ml) and ethyl acetate II (100ml), arid the layers separated. The aqueous phase was extracted with ethyl acetate1 (2x100ml), the combined organic solutions dried (MgS04) and evaporated 'under reduced pressure to afford the sub-title compound as a brown solid! 6.41g; Found : C, 41.27; H, 5.33; N, 11.11. C13E20BiN3O3S requires C, 41.35; H, 5.28; N, 10.99%; 5 (CDC13, 300MHz) : 1.06 (3H, t), 1.48 (3H, t), 2.42 (2H, q), 2.56 (4H, m), 3.09 (4H, m), 4.54 (2H, q), 8.10 (1H, s), 8.46 (1H, s); LRMS : m/z 378, 380 (M+l)+. 3(f) Pyridine 2-ethoxv-5-(4-ethvlpiperazin-l-vlsulphonvl)-3-carboxylic '! t . acid ethyl ester WO 01/98284 PCT7IB01/01050 A mixture of the product from stage 3(e) (6.40g, 16.92mmol), tiiemylamine (12ml, 86.1mmol), and palladium (0) liis(triphenylphosphine) in ethanol (60ml) was heated at 100°C and 200 psi, under a carbon monoxide atmosphereifor 18 hours, then cooled. The reaction mixture was evaporated under reduced pressure and the residue purified by column chromatography on silica gel, using an elution gradient of dichloromemane-methanol (100:0 to .97:3) to afford the sub-title compound as an orange oil, 6.2g; 8 (CDC13) 300MHz) : '1.02 (3H, t), 1.39 (3H, t), 1.45 (3H, t), 2.40 (2H, q), 2.54 (4H, m), 3.08 (4H, m), 4.38 (2H, q), 4.55 (2H, q), 8.37 (1H, s), 8.62 (1H, s); LRMS : m/z 372 (M+lf - • 3(g) Pyridine 2-ethoxv-5-(4-ethvlpiperazin-l-ylsulphonvl)-3-carboxvlic acid i WO 01/98284 PCT/IB01/01050 A mixture of the product from stage 3(f) (4.96g, 13.35mrn.ol) and aqueous sodium hydroxide solution (25ml, 2N, 50.0mmol) in ethanol (25ml) was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to half it's volume, washed with ether and acidified to pH 5 using 4N hydrochloric acid. The aqueous solution was extracted with dichloromethane (3x30ml), the combined organic extracts dried (MgS04) and evaporated under reduced pressure to afford the sub-title compound as a tan coloured solid, 4.02g; 5 (DMSOd6> 300MHz) : 1.18 (3H, t), 1.37 (3H, t), 3.08 (2H, q), 3.17-3.35 (8H, m), 4.52 (2H, q), 8.30 (1H, s), 8.70 (1H, s), 3(h) ■4-r2-Ethoxy-5-(4-emvIprperazm-l-vlsulphonvl)pvridiri-3- .•'•■'•'■ i| ■ . vlcarboxarriidol-lH-3-ethylpvrazole-5-carboxamide N) o \rN- y H ) o=s=o 0 A solution of 4-amino-3-ethyl-lH-pyrazole-5-carboxamide (WO 9849166, preparation i;8) (9.2g, 59.8mmol) in N,N-dimemylfoimamide (60ml) was added to a solution of the product from stage g) (21.7g, 62.9mmol), 1-hydroxybenzptriazole hydrate (10. Ig, 66.0mmol) and triemylarnine (13.15ml, 94.3mmol) in dichloromethane (240ml). l-(3-Dimemylaminopropyl)-3-emylcarbodiimide hydrochloride (13.26g, 69.2mmol) was added and the reaction stirred at room temperature for 6 hours. The ;dichloromethane was removed under reduced pressure, the remaining solution poured into ethyl acetate (400ml), and this mixture washed withi aqueous sodium bicarbonate solution (400ml). The resulting WO 01/98284 PCT/TB01/01050 crystalline precipitate was filtered, washed with ethyl acetate and dried under vacuum, to afford the sub-title compound, as a white powder, 22g; 8 (CDCI3+I drop DMSOd6) 0.96 (3H, t), 1.18 (3H, t), 1.50 (3H, t), 2.25-2.56 (6H, m), 2.|84 (2H, q), 3.00 (4H, m), 4.70 (2H, q), 5.60 (1H, br s), 6.78 (1H, br s), 8.56 JlH, d), 8.76 (1H, d), 10.59 (1H, s), 12.10-12.30 (1H, s); LRMS: , m/z480(M+l)+. 3 (i) 2-Methox veth vl-4- r2-ethoxv-5-f4-eth vlpiperazin-1 - vlsu3!phonvl)pvndin-3-vlcarboxamido1-3-ethvlpyrazole-5-carboxamide l-Bromo-2-methoxyethane (1.72mrnol) was added to a.solution of the product from stage 3(h) (750mg, 1.56mmol) and caesium carbonate (1.12g, 3.44mmol) in N,N-dimethylformarnide (15ml) and the reaction stirred at 60° C for 18 hoiirs. The cooled mixture was partitioned between water and ethyl acetate, and; the layers separated. The organic layer was dried (MgS04), i concentrated under reduced pressure and azeotroped with toluene to give a solid. This 'product was recrystaUised from ether, to afford the sub-title compound as a white solid. 5(CDC13): 1:04 (3H, t), 1.22 (3H, t), 1.60 (3H, t), 2.44 (2H, q), 2.54 (4H, m), 2.96 (2H, q); 3.12 (4H, m), 3.36 (3H, s), 3.81 (2H, t), 4.27 (2H, t), 4.80(2H, q), 5.35(lH,s), 6.68 (1H, s), 8.66 (1H, d), 8.86 (1H, d), 10.51 (1H, s). WO 01/98284 PCT/EBO1/01050 PCT / IB 0 1 / U 1 0 3 0 General Preparative Examples Preparation 1 2-Ethvl-2-ethoxv-5-(r4-ethvl-l-piperazinvlsulfonvl)pvridinoate - Compound IV wherein R3 & R4 = Et; A = N: G = CQ2H Preparation^ (la) 2-Hvdroxv-5-sulfonicotinic acid 2-Hydroxyr4cotinic acid (27Kg, 194.2mol) was added portionwise to 30% oleum (58.iKg) at 50°C over lhr. This caused an exotherm to 82°C. The reaction mixture was heated further to 140°C. After maintaining this temperature: for 12hrs the reactor contents were cooled to 15C and filtered. The filter jcake was then re-slurried with acetone (33Kg) at room temperature; filtered and dried to afford the sub-title compound (35.3Kg, 83%) as a \yhite solid. Decomposition pt 273°C. 5 (DMSOd6): 7.93 (1H, d), 8.42 (1H, d% m/z (Found:220 [M+H]+,.100%. CgHgNOgS requires 220.17). Preparation [(lb) Ethvl 2-hvdroxv-5-sulfonicotinoate 2-Hydroxy-5-sulfomcotmic acid (500g, 2.28mol) was dissolved in efhanol (2.5L) with1 stirring and heated to 80°C. After 30mins 0.5L of solvent was distilled off, then replaced with fresh ethanol (0.5L) and taken back to 80°C. After a further 60mins l.OL of solvent was distilled off, then replaced with fresh ethanol (l.OL) and taken back to 80°C. After a further 60mins l.OL of solvent washdistilled off, the reaction cooled to 22°C and stirred for 16hr. WO 01/98284 PCT/TB01/01050 The precipitated product was filtered, washed with ethanol (0.5L) and dried at 50°C under vacuum to afford the sub-title compound (416g, 74%) as a white solid. Decomposition pt 237°C. 5 (DMSOd6): 1.25 (3H, t), 4.19 (2H,q), 7.66 (1H, d), 8.13 (1H, d). m/z (Found:248 [M+H]+, 100%. C8H10NO6S requires 248.22). Preparation; (lc) Ethyl 2-chloTO-5-chlorosulfomcotinoa.te Ethyl 2-hydroxy-5-sulfomcotinoate (24.7g, O.lmol) was slurried in thionyl chloride (238g, 2.0mol) and dirnethylformamide (l.OmL) with stirring. The reaction mixture was then heated to reflux for 2.5hr. The bulk of. the thionyl chloride wajs removed under vacuum with residual thionyl chloride removed with a toluene azeotrope to afford the crude sub-title compound (30.7g, 108%) as aiyellow oil. 5 (CDC13): 1.46 (3H, t), 4.50 (2H, q), 8.72 (1H, d), 9.09 (1H, d). This was taken directly onto the next step. Preparation (Id^Ethyl 2-chloro-5-(4-ethvl-l-piperazinvlsulfonvlN> rdcotinoate Crude ethyl i2-chloro-5-chlorosulfonicotinoate (30.7g, O.lmol assumed) was ii dissolved in jethyl acetate (150mL) with stirring then ice cooled. To this was added a solution of N-emylpiperazine (11.4g, O.lmol) and triethylamine (22.5g, 0.22mol) in ethyl acetate (50mL), carefully over 30mins, keeping the internal temperature below 10°C. Once the addition was complete the reaction was allowed to warm to 22°C and stir for Ihr. The solid was filtered off and .the remaining filtrate was concentrated under vacuum to afford the crude sub-title compound (37.lg, 103%) as a crude yellow gum. 5 WO 01/98284 PCT/IB01/01050 PCI / IB u "I ' u i u ~ u (CDCI3): 1.10 (3H, t), 1.42 (3H, m), 2.50 (2H, m), 2.60 (4H, m), 3.19 (4H, m), 4.43 (2H, q), 8.40 (1H, d), 8.80 (1H, d). m/z (Found:362 [M+H]+, 100%. C14H2iClN304S requires 362.85). Preparation! rie^Ethvl2-ethoxv-5-(4-ethyl-l-piperazmvlsulfonvl)nicotiiioate A solution of ethyl 2-cKloro-5-(4-ethyl-l-piperazinylsulfonyl)nicotiiioate (36.1g, O.llmol) in ethanol (ISOmL) was cooled to 10°C with stirring. Sodium ethoxide (10.2g, 0.15mol) was added portionwise keeping the temperature below 20°C. The reaction mixture was then stirred at ambient temperature, for 18 hours. The precipitate was filtered off and water. . (180mL) added to the filtrate. The filtrate was then heated to 40°C for 1 hour. Ethanol (180mL) was then distilled off at ambient pressure and the remaining aqueous solution allowed to cool to ambient temperature. The precipitated product was then filtered off, washed with water and dried under vacuo at 50°C to afford the sub-title compound (12.6g, 34%) as a light brown; solid. M.p. 66-68°C. 5 (CDC13): 1.04 (3H, t), 1.39 (3H, t), 1.45 (3H, t), 2.41 (2H, q), 2.52 (4H, m), 3.08 (4H, m), 4.38 (2H, q), 2.57 (2H, q), 8.38 (1H, d), 8.61 (1H, d). m/z (Found: 372 [M+H]+, 100%. Cl6E26N305S 1 requires 372.46). Preparation (If) 2-Ethoxv-5-(4-ethvl-1 -piperazinvlsulfonyDnicomiic acid Ethyl 2-emoxy-5-(4-emyl-l-piperazmylsulfonyl)nicotinoate (10.2g, 0.0275mol), was dissolved in toluene (50mL) and a solution of sodium WO 01/98284 PCT/IB01/01050 hydroxide (l.lg, 0.0275mol) in water (20mL) added to it. This two phase mixture was then stirred vigorously at ambient temperature overnight. The aqueous phase was separated off and adjusted to pH=5.6 by addition of cone, hydrochloric acid. The precipitated product was slurried with ice cooling foil 15minutes, filtered, water washed and dried under vacuo at 50°C to afford the sub-title compound (4.1g, 43%) as an off-white solid. Mpt 206-207°C. 5 (bDCl3): 1.25 (3H, t), 1.39 (3H, t), (2H, q), 3.03 (4H, m), 3.25 (4H, m), 41150 (2H, q), 8.25 (1H, d), 8.56 (1H, d). m/z (Found:344 [M+H]+, 100%. Q4H22N3O5S requires 344.38). 1 This step is1, a simple hydrolysis and the yield of 43% is not optimum. The same hydrolysis was carried out in preparation 23 of PCT/IB 99/00519 - (which is incorporated herein by reference) and a more optimised yield of ■ ■ ' ' I! 88% was obtained for the hydrolysis. PreparationIJ (lg) Alternative Preparation for 2-Ethoxy-5-(4-ethvl-l-piperazinylsulfonvl)nicotinic acid (the compound of Preparation (If) -Telescoped process in toluene from ethyl 2-hvdroxv-5-sulfonicotinoate I, Ethyl 2-hydroxy-5-sulfonicotinoate (the compound of Preparation (lb)) (441.5g, 1.79mol) was dissolved in toluene (1.77L) and thionyl chloride (1.06Kg, 8.93moI) and dimethylformamide (71.3mL) were then added. The stirred suspension was then heated to reflux for 3 hours to yield a yellow solution. Thionyl chloride (2.87L) was then distilled with continual replacement iwith toluene (2.15L). The pale yellow solution was then cooled to 10°C and1 a stirred solution of N-ethylpiperazine (198.9g, 1.66mol) and triethylamine, (392.2g, 3.88mol) in toluene (700mL) added dropwise over WO 01/98284 PCT7IB01/01050 90 minutes keeping the reaction mixture below 10°C . The reaction was stirred at ambient temperature for 18 hours then washed with water (2 x 700mL) and brine (2 x 350mL). The toluene phase was azeotropically dried by distilling off 1750mL which was continuously replaced by dry toluene (1750mL).'The remaining brown solution was cooled to 10°C and sodium ethoxide (lii78.0g, 2.62moJ) was added portionwise keeping the temperature below 10°C. The reaction was then stirred at 10°C for 1 hour then allowed to warm to'ambient temperature and stirred for 18 hours. Sodium hydroxide (34.9g, *mol) dissolved in water (1.5L) was .then added to the toluene mixture and the 2 phase mixture was vigorously stirred for 18 hours at 40°C. Once cooled to ambient temperature the aqueous phase was separated off. To this was added cone, hydrochloric acid to pH=3 which precipitated a light brown solid which was granulated for 2 hour with ice cooling. The precipitate was filtered washed with water (300mL) -and dried under vacuo at 50°C tojkfford the sub-title compound (338.4g, 57.4%) as an off-white solid. Mpt J206-207°C. 5 (CDC13): 1.25 (3H, t), 1.39 (3H, t), 2.82 (2H, q), 3.03 (4H, m), 3.25 (4H, m), 4.50 (2H, q), 8.25 (IH, d), 8.56 (IH, d). m/z (Found:344;[M+H]+, 100%. Q4H22N3O5S requires 344.38). Preparation 2 2-ethoxy-5-(4-methvl-1 -piperazinylsulfonvDbenzonitrile. WO 01/98284 PCT/IB01/010S0 PCT / IB 0 1 / 0 ] 0 5 0 Trie&ylami&e (49.1 g, 0.485 Mol) was added to a slmr)> of 2-e&oxy-5-(4- methyl-l-piperazinylsulfonyl)benzamide (40.9 g, 0.125 Mol) in dichloromejjhane (200 mL) and this mixture was cooled to 0°C. Tiifluoroac'^tic anhydride (58.9 g, 0.28 Mol) was added dropwjse over 45 min and was washed in with DCM (25 mL) before the reaction was stirred li at ambient temperature for 18h. Water (125 mL) was added to the reaction ., ..II with cooling. The layers were separated and the organic phase was washed i' with water jbefore evaporation. The residue was stirred with ethyl acetate (150 mL) giving a c^stalline solid which was filtered off and dried under vacuum; 27(J4.g, 71%. m.p. = 130-131°C. M/Z = 310 (M+H); IH NMR • (300MHz, CDCIs): 1.55 (t, 3H), 2.30 (s, 3H), 2,50 (m, 4H), 3.06 (m, 4H), 4.26 (quart. !2H), 7.08 (d, IH), 7.90 (dd, IH), 7.97 (d, IH): . ■ Preparation 3 2-Ethoxy-N-hvdroxv-5-r(4-methvlpiperazin-l- yl)sulfonyl1benzenecarboxiimdanudme Hydroxylamiae hydrochloride (20.8 g, 0.3 Mol) was added to a stirred slurry WO 01/98284 PCT7IB01/01050 of 2-etho^-5-(4-methyl-l-piperazinylsulfonyl)benzonitrile (9.3 g, 0.03 Mol) in methanol (250 ml). To this mixture was added triemylamine (30.1 g, 0.3 Mol)'this was washed into the reaction with methanol (50 mL) to give a solution. The reaction was allowed to stir for 90h at room temperature before evaporation to low volume. Water (500 mL) was added and after 30 min stirring, the title compound was filtered off, washed with water and dried irnderj[vacuum to yield 8.0 g, 78%. m.p. = 183-185°C (decomp.); M/Z = 343 (M+H). 1H NMR (300MHz, DMSO-d6): 1,38 (t, 3H), 2.14 (s, 3H), 2.50 (m, 4H), 3.30 (m, 4H), 4.20 (quart. 2H), 5.74 (s, 2H), 7.29 (dd, 1H), 7.70 (m, 2H), 9.61 (s, 1H). Preparation 4 l-(4-Ethoxy-3-[5-(triflouromethvl)-l,2,4-oxadiazol-3-yllphenylsulfonyl}-4- methylpiperazine The A^-hydroxyamidine prepared in preparation 3 (6.0 g, 0.0175 Mol) was added to trifluoroacetic acid (17.5 mL) at room temperature. Trifluoroacetic anhydride (17.5 mL) was then added to give a clear solution and after 2h stirring at room temperature the reaction was evaporated at reduced WO 01/98284 PCT/IB01/01050 pressure. Toluene was added and then the mixture was re-evaporated. On stirring the; i residue with methanol the product crystallised and was filtered off, washed with methanol and dried under vacuum. This yielded 7.8. g 85% of the desired product; m.p. = 189-200°C (decomp.); M/Z = 421 (M+H). 1H NMR (loOMHz, DMSO-d6): 1.42 (t, 3H), 2.77 (s, 3H), 3.29 (br, m, 4H), 3.43 (br, m J4H), 4.37 (quart. 2H), 7.58 (d, 1H), 8.08 (dd, 1H), 8.23 (d, 1H). Preparation 5 ^-roi-hoxv-5-("4-methyl-1 -piperazmylsulfonvDberrzarnidine Water (4 ml) was added to a slurry of the compound prepared in preparation 4 (5.34 g, 0.01 Mol) in methanol (40 mL) at room temperature. The reaction rnixture was then treated with triethylamine (2 mL) followed by Raney Ni (0.5 g). The resultant mixture was hydrogenated for 5h at ambient temperature. After the catalyst had been filtered off, the filtrate was heated i to 90°C for' 10 min and was then evaporated at reduced pressure. The residue was re-evaporated from toluene before being subjected to WO 01/98284 PCT/EB01/01050 chromatography on silica gel eluting with toluene / methanol mixtures. Combination and evaporation of like fractions yielded 2.05 g (63%); M/Z = 327 (M+H);' 1H NMR (500 MHz CDC13/CD30D): 1.41 (t, 3H), 2.60 (s, 3H), 2.99 (br, in, 4H), 3.20 (br, m, 4H), 4.16 (quart. 2H), 7.10 (d, 1H), 7.77 (d, 1H), 7.82 (dd, 1H). Preparation 6 2-ethoxyr5-(4-memyl-l-piperazmylsulfonyl)benzamidine (Preparation 5 above) can also be prepared by the following method; Triemylalurmnium (20 mL of 2M solution in hexane) was added to ammonium bhloride (1.07 g, 0.2 Mol) slurried in toluene (20 mL) which had been pre-copled to 5°C. The reaction was stirred without cooling until there was no further gas evolution when the compound prepared in preparation 2 (3.09 g, 0.1!' Mol). was added. The mixture was stirred at 80°C for 40h. After cooling to room temperature silica gel (6 g) and dichloromethane (40 mL) were added and the mixture was stirred before filtration. The solids were washed with a methanol / dichloromethane mixture. The combined i' filtrate andilwashings were evaporated at reduced pressure to afford the product; 2.12 g 58%. Data as reported above. Preparation 7 2^emoxy-5-(4-ethyl-1 -piperazinylsulfonyDbenzonitrile. WO 01/98284 PCT7IB01/01050 Commercially available 2-ethoxybenzonitrile (25 g, 0.17 Mol) was added dropwise to an ice cooled mixture, of chlorosulfonic acid (50.8 mL, 0.765 i, ■ Mol) and thionyl chloride (L2.4 mL, 0.17 Mol) so as to keep the temperature below 10°C\: The reaction was then stirred at ambient temperature for 18h before being poured onto ice/water. This mixture was stirred lhr before the I ■ ... precipitated jmaterial was filtered off. The resultant solid was dissolved in acetone (300 mL) and triemylamine (25 mL, 0.179 Mol) was added followed by! a slow addition of N-ethylpiperazine (25 mL, 0.198 Mol). After being left at ambient temperature for 65h the mixture was evaporated and the residue i stirred with water (1 L) for 2h. The solids were filtered off, washed with water and dried before being chromatographed over silica gel using ethyl alcetate methanol mixtures. Combination and evaporation of lite fractions yielded 9.8 g, 17.8% of the title compound. Melting point = 86- 88°C. M/Z:.= 324 (M+H). 300MHz Proton NMR (CDC13); 1.06 (t, 3H), 1.55 (t, 3H)„2.43 (q, 2H), 2.54 (m, 4H), 3.06 (m, 4H), 4.25 (q, 2H), 7.08 (d, 1H), 7.90 (dii, 1H), 7.97 (d,lH). Preparation 8 2-'ethoxv-5-(4-ethvl-1 -piperazinylsulfonvDbenzamidine. WO 01/98284 PCT/IBO1/01050 Trimemylaliiminium (10 mL, 2 Moliar solution in hexanes) was added dropwise tola slurry of ammonium chloride (1.07 g, 0.02 Mol) in toluene (15 mL) at 0°C. The mixture was stirred without cooling until gas evolution stopped. 2-emoxy-5-(4-emyl4-pipera2inylsulfonyl)benzonitrile (the compound of Preparation 7) (3.23 g, 0.01 Mol) was then added and was washed in with toluene (5 mL) before the reaction was stirred at 80°C for 40h. After cooling to room temperature silica gel (15 g) and dichloromethane (100 mL) were added. The mixture was then filtered and the solids were washed with dichloromethane / methanol mixtures. The combined filtrate and washings were evaporated and the residue was chromatographed over silica gel using dichloromethane methanol mixtures to afford 1.08 g, 28.6% of the title compound. M/Z = found 341 (M+H). 1H NMR (CD3OD) 1.28 (t, 3H) 1.49 (t, 3H) 2.97 (q, 2H) 3.14 (br, s, 4H) 3.33(br, s, 4H) 4.32 (q, 2H) 7.45(d, 1H) 7.96 (d, 1H) 8.05 (dd, 1H). The compounds of preparations 7 and 8 can also be used in the preparation of the compounds of published international application W099/24433) according to a further aspect of the process of the present invention and in WO 01/98284 PCT/IB01/01050 particular ;to prepare 2-[2-Ethoxy-5-(4-ethyl-piperazin-l-yl-l-sulphonyl)- phenyl]-5-methyl-7-propyl-3H-inndazo[5J-jG[l,2,4]triazin-4-one also known as l-[[3-(3,4-dihydto-5-methyl-4-oxo-7-prop3'Hrnidazo[5,l-/]]-(2j'-triazin-2-yli)-4-ethoxyphenyl]sulphonyl] -4-ethylpiperazine (the compound of example's 20, 19, 337 and 336 of W099/24433). '! I WE CLAIM: 1. A proce'ss for the production of a compound of general formula I: wherein A represents CH or N; R1 represents linear C1-3 alkyl, which alkyl group is optionally interrupted by an oxygen atom, or is optionally terminated by a 2-pyridinyl group; R2 represents I(C1-4 alkyl; R3 represents alkyl, which alkyl group is optionally interrupted by an oxygen atom; R4 represents JC1.3 alkyl; 1 which proces^ comprises reaction of a piperazinylsulfonyl compound of formula II wherein Rx represents -NH2, -NHRa, -N(Rb)Rc", -SRd, -SH, -0Re (in which groups Ra to, Re each independently represent C1-3 alkyl, which alkyl group is optionally interrupted by an oxygen atom, or is optionally terminated by a 2-pyridinyl group or halo; with an amino: pyrazole carboxamide of general formula III wherein R1 and R2 are as defined above. 2. A process as claimed in Claim 1, wherein R2 represents linear C2-3 alkyl. 3. *A process as claimed in Claim 1, wherein R3 represents linear or branched C2-4 alkyl, which alkyl group is optionally interrupted by an oxygen atom. 4. A process as claimed in Claim 1, wherein R4 represents C1-2 alkyl. 5. A process as claimed in any one of the preceding claims, wherein the compound'lis selected from sildenafil, or any one of the following four compounds. 6. A proces's as claimed in Claim 1, wherein Rx represents -NHRa, -N(Rb)RC, -SRd J-SH or -ORe . 7. A process as claimed in Claim 6, wherein Rx represents ethoxy. 8. A process as claimed in any one of the preceding claims, wherein the reaction is carried out in the presence of a solvent system that includes an aromatic hydrocarbon, chlorobenzene or a solvent of formula RXH, wherein Rx is as claimed in Claims 1. I1 9. A process as claimed in Claim 8, wherein the solvent is toluene, xylene, chlorobenzene or ethanol. 10. A process as claimed in Claim 8 or Claim 9, wherein the reaction is carried out at reflux temperature. 11. A process as claimed in any one of the preceding claims, wherein the compound !of formula II is prepared by way of reaction of a compound of formula IV iv wherein G represents a carboxylic acid group (-C(O)OH) or a derivative thereof, and A, R3 and R4 are as defined in any one of Claims 1 and 6 to II 10 (as appropriate), with an appropriate reagent for converting the group G to a -C(RX)=NH group, wherein Rx is as claimed in any one of Claims 1. 12. A process as claimed in Claim 11, wherein, in the compound of formula IV, C(=NORf)NR«2 in Claim 1. ]he group G represents -CN, -C(ORe)3, -C(0)NH2 or -wherein Rf represents H or Ci-6 alkyl and Re is as defined 13. A process as claimed in Claim 12-, wherein, when Rx represents ORe (wherein Re represents Ci-6 alkyl (optionally interrupted by O), alkylHet or alkylaryl); (a) a corresponding compound of formula IV in which G represents -CN is reacted with an alcohol of formula VA, RaOH VA wherein RQ represents Ci-6 alkyl (optionally interrupted by O), alkylHet or alkylaryl, and' acid; Het is as defined in Claim 1, in the presence of a pro tic (b) a corresponding compound of formula IV in which G represents - C(0)NH2 is reacted with an appropriate alkylating agent of formula VB. Ra -Z1 VB n wherein Z1 represents a leaving group and RQ is as defined above; or (c) a corresponding compound of formula IV in which G represents -C(ORQ)3, wherein RQ is as defined above, is reacted with ammonia, or an N-protected derivative thereof. 14. A process as claimed in Claim 12, wherein, when Rx represents QRe (wherein Re represents Het or aryl), a corresponding compound of formula IV in which G represents -CN is reacted with a compound of formula VC, RpOH VC wherein Rp represents Het or aryl, and Het is as defined in Claim 1. 15. A proces[s as claimed in Claim 12, wherein, when Rx represents -NH2: (a) a corresponding compound of formula IV in which G represents -CN is reacted with hydrazine, hydroxy- lamine or O-lower hydroxylamine, followed by reduction of the resultant intermediate under standard conditions; or ;' (b) a corresponding compound of formula IV in which G represents - C(=N0R£)NR2, iwherein Rf is as defined in Claim 18, is reduced under standard condition. 16. A process as claimed in Claim 12, wherein, when Rx represents - NH2, -NHRa or -N(Rb)Rc, a corresponding compound of formula IV in which G represents -CN is reacted with a compound of formula VD, HN(Rx)(Re) VD wherein Rx an'd Re independently represent H or Ra, and Ra is as claimed in Claim 1. 17. A process as claimed in Claim 12, wherein, when Rx represents - SH: (a) a corresponding compound of formula IV in which G represents - CN is reacted with hydrogen sulfide; or (b) a corresponding compound of formula IV in which G represents - C(0)NH2 is reacted with a reagent that effects oxygen-sulfur exchange. 18. A process as claimed in Claim 12, wherein, when Rx represents - SRd, a corresponding compound of formula IV in which G represents -CN is reacted with a compound of formula VE, RdSH VE wherein Rd is as claimed in Claim 1. 19. A process as claimed in Claim 12, wherein, when Rx represents halo, a corresponding compound of formula IV in which G represents -C(0)NH2 is reacted with a halogenating agent. 20. A process as claimed in any one of Claims 1 to 10, wherein the compound of formula II is prepared by way of reaction of another compound of formula II with a reagent that will convert one Rx group to another, wherein Rx is as defined in Claim 1. 21. A process as claimed in Claim 20, wherein, when Rx represents ORe (wherein corresponding reacted with a' l Re represents Ci-6 alkyl, alkylHet or alkylaryl), a compound of formula II in which Rx represents CI is compound of formula VA, as defined in Claim 13. 22. A process as claimed in Claim 20, wherein, when Rx represents -NH2, -NHRa or -N(Rb)Rc, a corresponding compound of formula II in which Rx represents CI, -SH, -SRd or -ORe, wherein Rd and Re are as defined in Claim 1, is reacted with an appropriate compound of formula VD, as defined in Claim 16, or an acid addition salt thereof. 23. A process as claimed in Claim 20; wherein, when Rx represents SRd, a corresponding compound of formula IV in which Rx represents SH is reacted with a compound of formula VF, Rd-Z2 VF wherein Z2 represents a leaving group and Rd is as defined in Claim 1. 24. A process as claimed in any one of Claims 11 to 19, wherein the compound of formula VI, formula IV is prepared by reaction of a compound of wherein L1 is a leaving group and A, G and R3 are as defined in any one of Claims 1, 3, 5, 11 and 12 (as appropriate), with a compound of formula VII, wherein R4 is as defined in any one of Claims 1 and 5. 25. A process as claimed in Claim 24, wherein the compound of formula VI is prepared by reaction of a compound of formula VIII, wherein A, G alnd R3 are as defined in any one of Claims 1, 3, 5, 11 and 12 (as appropriate), with a reagent that may be used for the introduction of a -SO2L1 gropp into an aromatic or heteroaromatic ring system. 26. A process as claimed in any one of Claims 11 to 18, wherein the j compound of formula IV is one in which G represents -CN or -C(0)NH2, and is prepared by reaction of a compound of formula IX, wherein Q represents -CN or -C(0)NH2, L2 represents a leaving group and A and R4 are as defined in any one of Claims 1 and 5, with a compound that will provide the group R30. 27. A process as claimed in Claim 26, wherein the compound that will provide the group R30 is a Ci-6 alkyl alcohol. 28. A process as claimed in Claim 26 or 27, wherein the leaving group L2 is chloro. 29. A process as claimed in any one of Claims 26 to 28, wherein the compound of formula X, formula IX is prepared by reaction of a compound of wherein Q andjiL2 are as defined in Claim 26, and A is as defined in Claim 1, with a compound of formula VII as defined in Claim 24. 30. A process as claimed in any one of Claims 11 to 18, wherein the compound of formula IV is one in which G represents -CN, and is prepared by dehydration of a corresponding compound of formula IV in which G represents -C(0)NH2. 31. A process as claimed in any one of Claims 11 to 13, 17 and 19, wherein the compound of formula IV in which G represents -C(0)NH2 is prepared from a corresponding compound of formula IV in which G represents -C(O)OH by reaction with ammonia or a derivative thereof. Dated this 11th day of November, 2002. JAWANTA PAL OF REMFRY & SAGAR ATTORNEY FOR THE APPLICANTS

Documents:

in-pct-2002-01584-mum-cancelled pages(17-03-2006).pdf

in-pct-2002-01584-mum-cancelled pages(17-3-2006).pdf

in-pct-2002-01584-mum-claims(11-11-2002).pdf

in-pct-2002-01584-mum-claims(granted)-(17-03-2006).doc

in-pct-2002-01584-mum-claims(granted)-(17-03-2006).pdf

in-pct-2002-01584-mum-correspondence 1(8-10-2002).pdf

IN-PCT-2002-01584-MUM-CORRESPONDENCE 2(24-11-2005).pdf

in-pct-2002-01584-mum-correspondence(17-03-2006).pdf

in-pct-2002-01584-mum-correspondence(ipo)-(08-03-2007).pdf

in-pct-2002-01584-mum-correspondence(ipo)-(20-6-2007).pdf

in-pct-2002-01584-mum-description(complete)-(11-11-2002).pdf

in-pct-2002-01584-mum-form 18(28-02-2005).pdf

in-pct-2002-01584-mum-form 1a(11-11-2002).pdf

in-pct-2002-01584-mum-form 2(11-11-2002).pdf

in-pct-2002-01584-mum-form 2(granted)-(17-03-2006).doc

in-pct-2002-01584-mum-form 2(granted)-(17-03-2006).pdf

in-pct-2002-01584-mum-form 2(title page)-(11-11-2002).pdf

in-pct-2002-01584-mum-form 3(11-11-2002).pdf

in-pct-2002-01584-mum-form 3(24-11-2005).pdf

in-pct-2002-01584-mum-form 4(21-12-2005).pdf

in-pct-2002-01584-mum-form 5(11-11-2002).pdf

in-pct-2002-01584-mum-form-pct-ipea-409(11-11-2002).pdf

in-pct-2002-01584-mum-form-pct-isa-210(11-11-2002).pdf

in-pct-2002-01584-mum-other(13-04-2007).pdf

in-pct-2002-01584-mum-other(24-11-2005).pdf

in-pct-2002-01584-mum-petition under rule 137(24-11-2005).pdf

in-pct-2002-01584-mum-petition under rule 138(24-11-2005).pdf

in-pct-2002-01584-mum-power of attorney(11-11-2001).pdf

in-pct-2002-01584-mum-power of attorney(24-11-2005).pdf

IN-PCT-2002-01584-MUM-POWER OF AUTHORITY(11-11-2001).pdf

in-pct-2002-01584-mum-specification(amanded)-(24-11-2005).pdf