Title of Invention

2,3,4,5-TETRAHYDROBENZO[F][1,4] OXAZEPINE-5-CARBOXYLIC ACID AMIDE DERIVATIVES

Abstract The invention relates to benzoxazepinone derivatives of formula (I) wherein R<1> is hydrogen, lower alkoxy, halogen or -NR'R"; n is 1 or 2; R',R" are independently from each other hydrogen or lower alkyl; R<2> is hydrogen, lower alkyl, -(CH2)m-cycloalkyl, -(CH2)m-phenyl or -(CH2)m-O-lower alkyl; m is 0lor 2; R<3> is lower alkyl, -(CH2)m-C(0)0-lower alkyl, cycloalkyl or -(CH2)m-phenyl, which is unsusbtituted or substituted by one or two substituents, selected from the group consisting of halogen or lower alkyl; R<4> is -(CH2)omicron-phenyl, which is unsusbtituted or substituted by one or two substituents, selected from the group consisting of halogen, trifluoromethyl, -NR'R", nitro or _SO2NH2, or is -cycloalkyl, unsubstituted or substituted by phenyl, or is - (CR'R"omicron-heterocyclyl, selected from the group defined in claim 1 and o is 1 or 2; and to pharmaceutically suitable acid addition salts thereof. These compounds are good gamma-secretase inhibitors for the treatment of Alzheimer's disease.
Full Text

2,3,4,5-Tetrahydroben2o[f|[l,4]oxazepine-5-carboxylic acid amide derivatives as gamma-secretase inhibitors for the treatment of Alzheimer's disease
The invention relates to benzoxazepinone derivatives of formula




and o is 1 or 2;
and to pharmaceutically suitable acid addition salts thereof with the exception of 4-benzyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxyiic acid phenethyl-amide, 4-benzyl-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide, 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid phenethyl-amide and 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-S-carboxylic acid butylamide.
The excluded compounds have been specifically described in /. Org. Chem., 199% 64, 1074-1076 for a process using bifunktional starting materials containing aldehyde and carboxylic acid.
As used herein, the term "lower alkyl" denotes a saturated straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, 2-butyl, t-butyl and the like. Preferred lower alkyl groups are groups with 1-4 carbon atoms.
The term "cycloalkyl" denotes a saturated carbocyclic group, containing 3-7 carbon atoms.
The term "halogen" denotes chlorine, iodine, fluorine and bromine.
The term "lower alkoxy" denotes a group wherein the alkyl residues is as defined above, and which is attached via an oxygen atom.

The term "pharmaceutically acceptable acid addition salts" embraces salts with inorganic and organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methane-sulfonic acid, p-toluenesulfonic acid and the like.

It has b een found that the compounds of general formula I are y-secretase
inhibitors and the related compounds-may be useful in the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is the most common cause of dementia in later life. Pathologically AD is characterized by the deposition in the brain of amyloid in extracellular plaques and intracellular neurofibrillary tangles. The amyloid plaques are mainly composed of amyloid peptides (Abeta peptides) which originate from the (3-Amyloid Precursor Protein (APP) by a series of proteolytic cleavage steps. Several forms of APP have been identified of which the most abundant are proteins of 695, 751 and 770 amino acids length. They all arise from a single gene through differential splicing. The Abeta peptides are derived from the same domain of the APP but differ at their N- and C-termini, the main species are of 40 and 42 amino-acid length.
Abeta peptides are produced from APP through the sequential action of 2 proteolytic enzymes termed [3- and y-secretase. (3-Secretase cleaves first in the extracellular domain of APP just outside of the trans-membrane domain (TM) to produce a C-terminal fragment of APP containing the TM- and cytoplasmatic domain
(CTF(3). CTF(3 is the substrate for y-secretase which cleaves at several adjacent positions
within the TM to produce the A peptides and the cytoplasmic fragment. The majority of
Abeta peptides is of 40 amino acids length (Ap40), a minor species carries 2 additional amino acids at its C-terminus. Latter is supposed to be the more pathogenic amyloid peptide.
The -secretase is a typical aspartyl protease. The y-secretase is a proteolytic activity consisting of several proteins, its exact composition is incompletely understood. However, the presenilins are essential components of this activity and may represent a new group of atypical aspartyl proteases which cleave within the TM of their substates and which are themselves polytopic membrane proteins. Other essential components of
y-secretase may be nicastrin and the products of the aphl and pen-2 genes. Proven
substrates for y-secretase are the APP and the proteins of the Notch receptor family,
however, y-secretase has a loose substrate specificity and may cleave further membrane proteins unrelated to APP and Notch.

The y-secretase activity is absolutely required for the production of Abeta peptides. This has been shown both by genetic means, i.e., ablation of the presenilin genes and by low-molecular-weight inhibitory compounds. Since according to the amyloid hypothesis or AD the production and deposition of Abeta is the ultimate cause for the disease, it is thought that selective and potent inhibitors of y-secretase will be useful for the prevention and treatment of AD.
Thus, the compounds of this invention will be useful treating AD by blocking the activity of y-secretase and reducing or preventing the formation of the various amyloidogenic Abeta peptides.
Numerous documents describe the current knowledge on y-secretase inhibition, for example the following publications:
Nature Reviews/Neuroscience, Vol. 3, April 2002/281, Biochemical Society Transactions (2002), Vol. 30. part 4, Current Topics in Medicinal Chemistry, 2002, 2, 371-383, Current Medicinal Chemistry, 2002, Vol. 9, No. 11, 1087-1106, Drug Development Research, 56, 211-227, 2002, Drug Discovery Today, Vol. 6, No. 9, May 2001,459-462, FEBS Letters, 483, (2000), 6-10, Science, Vol. 297, 353-356, July 2002 and
Journ. of Medicinal Chemistry, Vol. 44, No. 13,2001, 2039-2060.
i Objects of the present invention are the compounds of formula I per se, the use of
compounds of formulas I and their pharmaceutically acceptable salts for the manufacture of medicaments for the treatment of diseases, related to the y-secretase inhibition, their manufacture, medicaments based on a compound in accordance with the invention and their production as well as the use of compounds of formula I in the control or prevention of Alzheimer's disease.
A further object of the invention are all forms of optically pure enantiomers, recemates or diastereomeric mixtures for compounds of formulas I.
The most preferred compounds are those, wherein R is lower alkyl. Especially preferred are compounds of this group, wherein R is cycloalkyl and R is -(CH2)0-phenyl, substituted by di-halogen or -NR'R", or is tetrahydro-pyran-4-yl, or is - tetrahydro-naphthalen-1-yl or is -(CH2)0-pyridin-3-yl. The following specific compounds relate to these groups:



9-ethox7-2-isopropyl-4-[2-(^^
benzo[f] [l34]oxazepine-5-carboxyiic acid tert-butylamide and
7-cWoro-4-cydopentyl-2-ethyl-3-oxo-2,3,4,5^
carboxylic acid tert-butylamide and
4-benzo[13]dioxol-5-yknethyl-8-dietiylamino-2-isopropyl-3-oxo-2?3J4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide and
4-(l-benzyl-piperidin-4-yl)-2-isopropyl-3-oxo-2,3J4>5-tetrahydro-benzo[f] [l,,4]oxazepine-5-carboxylic acid tert-butylamide.
Preferred are further compounds with R being lower alkyl, wherein R is-(CH2)m-phenyl and R4 is cycloalkyl. The following specific compound relate to this group:
7-chloro-4-cyclohexyl-2-isopropyl-3-oxo-2)3)4,5-tetrahydro-benzo[fj[lJ4]oxazepine-5-carboxylic acid benzylamide.
Preferred are farther compounds with R being lower alkyl, wherein R is -(CH2)m-C(0)0-lower alkyl and R4 is -(CH2)0-phenyl, substituted by CF3 or halogen. The following specific compounds relate to these groups: ([7-chloro-2-isopropyl-3-oxo-4-(3-trifluoromethyl-benzyl)-273,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amiiio}~acetic acidtert-butyl ester and i j[7-bromo-4-(2-chloro-benzyl)-2-isopropyl-9-methoxy-3-oxo-23?4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester.
The present compounds of formulas I and their pharmaceutically acceptable salts (
can be prepared by methods known in the art, for example, by processes described below, > which processes comprise
a) reacting a compound of formula

with a compound of formula
R4-NH2 III

and with a compound of formula

to a compound of formula

and
if desired, converting the compounds obtained into pharmaceutically acceptable acid addition salts.
The compounds of formula I maybe prepared in accordance with the following scheme 1:

In this scheme R1 to R are as described above.
A general synthesis of the benzoxazepinone skeleton is described in Zhang et al.: J. Org. Chem. 1999, 64, 1074 ff. The corresponding o-hydroxybenzaldehyde (V) is reacted with the alpha-bromocarboxylic acid alkylester (VI) to the 2-formylphenoxyacetic acid alkylester (VII), which is subsequently saponified to the 2-formylphenoxyacetic acid (II).

This acid is reacted with the amine (III) and isonitrile (IV) in an Ugi-type reaction to the benzoxazepinone derivative of formula I.
The starting materials (hydroxybenzaldehyde V and a-bromoesters VI) are commercial available or may be prepared in accordance with known methods.
The detailed description can be found below and in Examples 1 - 196.
Some compounds of formula I may be converted to a corresponding acid addition salt, for example compounds, containing an amine group.
The conversion is accomplished by treatment with at least a stoichiometric amount of an appropriate acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids suchas acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, efhanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. Typically, the free base is dissolved in an inert organic solvent such as diethyl ether, ethyl acetate, chloroform, ethanol or methanol and the like, and the acid added in a similar solvent. The temperature is maintained between 0 °C and 50 °C. The resulting salt precipitates spontaneously or maybe brought out of solution with a less polar solvent.
The acid addition salts of compounds of formula I maybe converted to the corresponding free bases by treatment with at least a stoichiometric equivalent of a suitable base such as sodium or potassium hydroxide, potassium carbonate, sodium bicarbonate, ammonia, and the like.
The compounds of formulas I and their pharmaceutically usable addition salts possess valuable pharmacological properties. Specifically, it has been found that the
compounds of the present invention may inhibit the y-secretase.
The compounds were investigated in accordance with the test given hereinafter.
Description of y-secretase assay
The activity of test compounds can be evaluated in assays which measure the proteolytic cleavage of suitable substrates by y-secretase activity. These can be cellular
assays where e.g., a substrate of the y-secretase is fused in its cytoplasmic domain to a transcription factor. Cells are transfected with this fusion gene and a reporter gene, e.g., firefly luciferase, which expression is enhanced by the transcription factor. Cleavage of

the fused substrate by y-secretase will lead to expression of the reporter gene which can be monitored in appropriate assays. The y-secretase activity can also be determined in cell-free in vitro asays where e.g., a cell lysate containing the y-secretase complex is incubated with a suitable APP-derived substrate which is cleaved to the Abeta peptides. The amount of produced peptides can be determined with specific ELISA assays. Cell lines of neuronal origin secrete Abeta peptides which can be measured with the specific
ELISA assay. Treatment with compounds which inhibit y-secretase leads to a reduction of secreted Abeta thus providing a measure of inhibition.
The in vitro assay of y-secretase activity uses a HEK293 membrane fraction as a source of
y-secretase and a recombinant APP substrate. Latter consist of the C-terminal 100 amino acids of human APP fused to a 6xHistidin tail for purification which is expressed in E.coli in a regulatable expression vector, e.g. pEtl5. This recombinant protein corresponds to
the truncated APP fragment which results after y-secretase cleavage of the extracellular
domain and which constitutes the y-secretase substrate. The assay principle is described in Li YM et al, PNAS 97(11), 6138-6143 (2000). Hek293 cells are mechanically disrupted and the microsomal fraction is isolated by differential centrifiigation. The membranes are solubilized in detergent (0.25 % CHAPSO) and incubated with the APP substrate. The
Abeta peptides which are produced by y-secretase cleavage of the substrate are detected by specific ELISA assays as described (Brockhaus M et al, Neuroreport 9(7), 1481-1486 (1998).
The preferred compounds show a ICso-T.O. In the list below are described some data to the y-secretase inhibition:


1
I
The compounds of formula I and the pharmaceutically acceptable salts of the compounds of formula I can be used as medicaments, e.g. in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions. The administration can, however, also be effected rectally, e.g. in the form of suppositories, parenterally, e.g. in the form of injection solutions.
The compounds of formula I can be processed with pharmaceutically inert,
inorganic or organic carriers for the production of pharmaceutical preparations. Lactose,
corn starch or derivatives thereof, talc, stearic acids or its salts and the like can be used,
for example, as such carriers for tablets, coated tablets, dragees and hard gelatine
capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes,
fats, semi-solid and liquid polyols and the like. Depending on the nature of the active
substance no carriers are, however, usually required in the case of soft gelatine capsules.
Suitable carriers for the production of solutions and syrups are, for example, water, polyols, glycerol, vegetable oil and the like. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like.
The pharmaceutical preparations can, moreover, contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying ' the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances.
Medicaments containing a compound of formula I or a pharmaceutically acceptable salt thereof and a therapeutically inert carrier are also an object of the present invention, as is a process for their production, which comprises bringing one or more compounds of formula I and/or pharmaceutically acceptable acid addition salts and, if

desired, one or more other therapeutically valuable substances into a galenical administration form together with one or more therapeutically inert carriers.
In accordance with the invention compounds of formula I as well as their pharmaceutical^ acceptable salts are useful in the control or prevention of illnesses based on the inhibition of the y-secretase, such as of Alzheimer's disease.
The dosage can vary within wide limits and will, of course, have to be adjusted to the individual requirements in each particular case. In the case of oral administration the dosage for adults can vary from about 0.01 mg to about 1000 mg per day of a compound of general formula I or of the corresponding amount of a pharmaceutically acceptable salt thereof. The daily dosage may be administered as single dose or in divided doses and, in addition, the upper limit can also be exceeded when this is found to be indicated.

Manufacturing Procedure
_ _.g..
1. Mix items 1, 2, 3 and 4 and granulate with purified water.
2. Dry the granules at 50°C.
3. Pass the granules through suitable milling equipment.
4. Add item 5 and mix for three minutes; compress on a suitable press.



The following examples illustrate the present invention without limiting it. The examples are compounds which can exist in the form of diastereomeric mixtures, as racemates, or as optically pure compounds.
Example 1
7-Bromo-4-(2,6-difluoro-benzyl)-2-isopropyl-3-oxo-2>3>4)5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
a) 2-f4-Bromo-2-formyl-phenoxy)-3-methyl-butvricacid
To a solution of 0.67 g (3.3 mmol) 5-bromosalicylaldehyde in dimethylformamide (6 ml) 0.2 g sodium hydride (60 % suspension in mineral oil, 5 mmol) was added in small portions at 0 °C. After stirring for about half an hour 1.05 g ethyl 2-bromo-3-methyl butyrat (5 mmol) was added slowly at room temperature and the mixture was allowed to stir at 90 °C overnight. After cooling ice water (25 ml) and IN sodium hydroxide solution was added until basic pH. The mixture was extracted three times with ethyl acetate, the comined organic layers were dried (MgSC4) and evaporated. Short column filtration of the residue yielded the ester that was used for the next step without characterisation.
The ester was dissolved in 2 ml of methanol and 2N aqueous sodium hydroxide solution
(2 ml) was added. After stirring for 1 hour at room temperature the solvent was removed
by rotary evaporation. Water (3 ml) and 4N hydrochloric acid was added until pH=4.
The mixture was extracted three times with ethyl acetate, the combined organic layers
were dried (MgSC^) and evaporated to yield 0.125 g of the title compound as colourless
oil.
MS m/e (%): 299.0 (M-H+, 93); 301.0 (M-H+, 100).
b) 7-Bromo-4-(2,6-difluoro-benzvl)-2-isopropvl-3-oxo-2,3>4,5-tetrahydro-
benzoFfl l"l,4loxazepine-5-carboxylic acid cyclohexylamide
To a solution of 0.12 g 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid (0.4 mmol) in dimethylsulfoxide (0.8 ml) 0.057 g 2,6-difluorobenzylamine (0.4 mmol) and 0.044 g cyclohexyl isocyanide (0.4 mmol) was added and the mixture was allowed to stir overnight. A 10 % aqueouos sodium chloride solution (5 ml) was added and the mixture was extracted three times with etyl acetate. The combined organic layers were dried (MgS04) and evaporated in vacuo. The residue was purified using column chromatography with ethylacetate / hexane (1:4) as eluent to yield 0.03 g of the title compound as light yellow foam.

MS m/e (%): 535.3 (M+H+, 100); 537.3 (M+H+, 95).
Example 2 7-Bromo-4-(2,6-difluoro-benzyl)-2-isopropyl-3-oxo-2>3,4)5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid 3,4-dichloro-benzylamide
The title compound was obtained in comparable yields according to the procedures described for example 1 using l>2-dichloro-4-isocyanomethyl-benzene instead of cyclohexyl isocyanide in step b). MS m/e (%): 629 (M+H20+H+, 58); 630 (M+H20+H+, 100);.
Example 3 7-Bromo-4-(2,6-difluoro-benzyl)-2-ethyl-3-oxo-2)3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
2,6-Difluorobenzylamine (51mg, 0.35mmol) and cyclohexylisocyanide (39 mg, 0.36 mmol) were added to a solution of 2-(4-bromo-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-3-methylbutyrat, 100 mg, 0.35 mmol) in methanol (0.5 ml). After stirring for 2h at r.t., the title compound was isolated (diastereomer 1 [inhibitorially active], retention time 2.09 min: 17.9 mg; diastereomer 2 [inhibitorially active], retention time 2.28 min, 7.3 mg, combined yield 14 %, MS: m/e = 521.1 [M+H+]) from the reaction mixture by reversed-phase, preparative HPLC (YMC CombiPrep C18 column
50x20mm, solvent gradient 5-95 % CH3CN in 0.1 % TFA(aq) over 6.0min, X = 230nm,
flow rate 40ml/min).
Example 4 7-Bromo-2-cyclohexylmethyl-4-(2,6-difluoro-benzyl)-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS: m/e = 589.4 [M-f-H+], was obtained in analogy to example 3 from 2-(4-bromo-2-formyl-phenoxy)-3-cyclohexyl-propionic acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-but)T:ic acid [example 1] from 2-bromo-3-cyclohexyl-propionic acid ethyl ester) as a mixture of diastereomers.
Example 5 7-Bromo-2-butyl-4-(2,6-difluoro-benzyl)-3-oxo-2,3,4,5-tetrahydro- • benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide

The title compound, MS: m/e = 549.4 [M+H+], was obtained in analogy to example 3 from 2-(4-bromo-2-formyl-phenoxy)-hexanoic acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from methyl 2-bromocaproate) as a mixture of diastereomers.
Example 6
7-Chloro-4-cyclohexyl-2-ethyl-3-oxo-2>3>4J5-tetrahydro-benzo[fj[l)4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS: m/e = 433.5 (M+HT), was obtained in analogy to example 3 from cyclohexylamine and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorily active).
Example 7 7-Chloro-4-(2-chloro-benzyl)-2-ethyl-3-oxo-2>3)4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS: m/e = 475.3 (M+H+), was obtained in analogy to example 3 from 2-chlorobenzylamine and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) two separable diastereomers (both inhibitorily active).
Example 8 7-Chloro-4-cyclobutyl-2-ethyl-3-oxo-2,3>4,5-tetrahydro-benzo[f][l>4]oxazepine-5-
carboxylic acid cyclohexylamide
The title compound, MS: m/e = 405.4 (M-f H+)> was obtained in analogy to example 3 from cyclobutylamine and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as a mixture of diastereomers.
Example 9 7-Chloro-4-cyclopentyl-2-ethyl-3-oxo-2>3,4J5-tetxahydro-benzo [f] [1,4] oxazepine-5-carboxylic acid cyclohexylamide

The title compound, MS: m/e = 419.4 (M+H+), was obtained in analogy to example 3 from cyclopentylamine and 2-(4-cUoro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyricacid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorily active).
Example 10 7-Chloro-2-ethyl-3-oxo-4-(tetrahydro-pyran-4-yl)-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS: m/e = 435.4 (M+H+), was obtained in analogy to example 3 from 4-aminotetrahydropyran and 2-(4-cUoro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorily active).
Example 11 7-Chloro-2-ethyl-3-oxo-4-(3-trifluoromethyl-benzyl)-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS: m/e = 509.3 (M+H+)> was obtained in analogy to example 3 from 3-txifluorobenzylamine and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorially active).
Example 12 7-Chloro-4-(2,6-difluoro-benzyl)-2-ethyl-3-oxo-2?3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS: m/e = 451.3 (M-f-H+), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, tert-butylisocyanide, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-Bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorially active).
Example 13 7-Chloro-4-cyclohexyl-2-ethyl-3-oxo-2,3)4?5-tetrahydro-benzo[f][l54]oxazepine-5-carboxylic acid tert-butylamide

The title compound, MS: m/e = 407.4 (M+H+), was obtained in analogy to example 3 from cyclohexylamine, fel-Butylisocyanide, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorily active).
Example 14 7-CHoro-4-(2-chloro-benzyl)-2-ethyl-3-oxo-2)3>4>5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS: m/e = 449.3 (M+H+), was obtained in analogy to example 3 from 2-chlorobenzylamine, tert-butylisocyanide, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorily active).
Example 15
7-Chloro-4-cyclobutyl-2-ethyl-3-oxo-2,3,4,5-tetrahydro-benzo [f] [1,4] oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS: m/e = 379.3 (M+H*), was obtained in analogy to example 3 from cyclobutylamine, tert-Butylisocyanide, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde).
Example 16
7-Chloro-4-cyclopentyl-2-ethyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid tert-butylamide
The tide compound MS: m/e = 393.3 (M+H+), was obtained in analogy to example 3 from cyclopentylamine, tat-Butylisocyanide, and2-(4-cUoro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-but)nic acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as two separable diastereomers (both inhibitorily active).
Example 17 7-Chloro-2-ethyl-3-oxo-4-(tetrahydro-pyran-4-yl)-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide

The title compound, MS: m/e = 409.3 (M+H+) , was obtained in analogy to example 3 from 4-aminotetrahydropyran, tert-Butylisocyanide, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde).
Example 18 7-Chloro-2-ethyl-3-oxo-4-(3-trifLuoromethyl-benzyl)-253)4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS: m/e = 483.5 (M+H+), was obtained in analogy to example 3 from 3-trifluoromethylbenzylamine, tert-butylisocyanide, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as a mixture of diastereomers.
Example 19 {[7-Chloro-4-(2,6-difluoro-benzyl)-2-ethyl-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The tide compound, MS: m/e = 509.3 (M+H+), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, Isocyano-acetic acid tert-butyl ester, and 2-(4-chloro-2-formyl-phenoxyj-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde).
Example 20 [ (7-Chloro-4-cyclohexyl-2-ethyl-3-oxo-2?3,4,5-tetrahydro-benzo [fj [ 1,4] oxazepine-5-carbonyl)-amino]-acetic acid tert-butyl ester
The title compound MS: m/e = 465.3 (A4+H+), was obtained in analogy to example 3 from cyclohexylamine, Isocyano-acetic acid tert-butyl ester, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as a mixture of diastereomers.
Example 21 [(7-CUoro-4-cyclobutyl-2-ethyl-3-oxo-2,3,4,5-telTahydxo-benzo[f][l,4]oxazepine-5-carbonyl)-amino]-acetic acid tert-butyl ester

The title compound, MS: m/e = 437.3 (M+H ), was obtained in analogy to example 3 from cyclobutylamine, Isocyano-acetic acid tert-butyl ester, and 2-(4-chloro-2-formyl-phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) as a mixture of diastereomers.
Example 22 [(7-Chloro-4-cyclopentyl-2-ethyl-3-oxo-2>3,4>5-tetrahydro-benzo[f][l)4]oxazepine-5-carbonyl)-amino]-acetic acid tert-butyl ester
The title compound, MS: m/e = 451.4 (M+ET), was obtained in analogy to example 3 from cyclopentylamine, Isocyano-acetic acid tert-butyl ester, and 2-(4-chloro-2-formyl~ phenoxy)-butyric acid (prepared in analogy to 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid [example 1] from ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde).
Example 23 7-Chloro-4-(2,6-difluoro-benzyl)-3-oxo-2)3J4)5-tetrahydro-benzo[fj[l)4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 449.14 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylarnine, (4-chloro-2-formyl-phenoxy)-acetic acid, and Isocyano-cyclohexane.
Example 24 4-(2,6-Difluoro-benzyl)-6,8-dimethoxy-3-oxo-2,3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 449.18 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, (2-formyl-3,5-dimethoxy-phenoxy)-acetic acid, and 2-Isocyano-2-methyl-propane.
Example 25 6>8-Dimethoxy-3-oxo-4-(l,2)3,4-tetrahydro-naphthalen-l-yl)-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 479.25 (M+l), was obtained in analogy to example 3 from 1,2,3,4-tetrahydro-naphthalen-l-ylamine, (2-formyl-3,5-dimethoxy-phenoxy)-acetic acid, and Isocyano-cyclohexane.

Example 26 7-Chloro-4-(4-chloro-2-fluoro-benzyl)-3-oxo-2>3>4>5-tetxaliydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 465.1 (M+l), was obtained in analogy to example 3 from 4-chloro-2-fluorobenzylamine, (4-chloro-2-formyl-phenoxy)-acetic acid, and isocyano-cyclohexane.
Example 27 4-(2,6-Difluoro-benzyl)-2-isopropyl-8-methoxy-3-oxo-2>3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 461.2 (M+l), was obtained in analogy to example 3
from 2,6-difluorobenzylamine, 2-(2-formyl-5-methox)'-phenoxy)-3-methyl-butyric acid,
and 2-isocyano-2-methyl-propane.
Example 28 2-Isopropyl-8-methoxy-3-oxo-4-(3-trifluoromethyl-benzyl)-2)3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 493.2 (M+l), was obtained in analogy to example 3
from 3-trifluoromethylbenzylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric
acid, and 2-isocyano-2-methyl-propane.
Example 29
4-[2-(5-Huoro-lH-indol-3-yl>^
tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 510.3 (M+l), was obtained in analogy to example 3 from2-(5-fluoro-lH-indol-3-yl)-l-methyl-ethylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 30 4-(4-Dimetiiylaixiino-benzyl)-2-isopropyl-3-oxo-2,3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 438.3 (M+l), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(2-formyl-phenox)0-3-niethyl-butyric acid, and ) 1 -isocyano-butane

Example 31
24sopropyl-4-[2-(5-nitro-pyridin-2-ylamino)-ethyl]-3-oxo-2)3)4J5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 496.2 (M+1) , was obtained in analogy to example 3 from 2-(5-nitro-pyridin-2-ylamino)-ethylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, andisocyano-cyclohexane.
Example 32 7-Bromo-4-(9H-fluoren-9-yl)-3-oxo-2>3J4)5-tetrahydro-benzo[f][l)4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 505.1 (M+1), was obtained in analogy to example 3 from 9H-fiuoren-9-ylamine, (4-bromo-2-formyl-phenoxy)-acetic acid, and 2-isocyano-2-methyl-propane.
Example 33 8-Diethylamino-4-(9H-fluoren-9-yl)-2-methyl-3-oxo-2,3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 512.3 (M+1), was obtained in analogy to example 3 from 9H-fluoren-9-ylamine, 2-(5-diethylamino-2-formyl-phenoxy)-propionic acid, and 2-isocyano-2-methyl-propane.
Example 34 7-Chloro-4-(2>6-difluoro-benzyl)-2-isopropyl-3-oxo-2,3)4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 465.2 (M+1), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 35 7-Chloro-4-(2,6-difl.uoro-benzyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 491.2 (M+1), was obtained in analogy to example 3 from 2,6-difLuorobenzylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 36 7-CUoro-4-(4-dimethylainino-ben2yl)-24sopropyl-3-oxo-23J4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 472.2 (M+l), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(4-cUoro-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 37 7-Chloro-2-isopropyl-4'(2-methylsulfanyl-ethyl)-3-oxo-2,3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 439.2 (M+l), was obtained in analogy to example 3 from 2-methylsulfanyl-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 38 7-Chloro-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2,3>4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 482.2 (M+l), was obtained in analogy to example 3 from 2-( lH-indol-3-yl)-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 39 7,9-Dichloro-4-(2?6-difluoro-benzyl)-2-methyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 497.11 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(2,4-dichloro-6-formyl-phenoxy)-propionic acid, and Isocyano-cyclohexane.
Example 40 7-Bromo-4-(2,6-difluoro-benzyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 509.12 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 41
7-Bromo-4-(2-cbloro-benzyl)-2-isopropyl-3-oxo-2,3J4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 533.2 (M+l), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(4-bromo-2-forinyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 42 4-(4-CUoro-2-fluoro-benzyl)-8-diethylam.ino-2-isopropyl-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid benzylamide
The title compound, MS m/e: 552.4 (M+l), was obtained in analogy to example 3 from 4-chloro-2-fluorobenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyanomethyl-benzene.
Example 43 7-Bromo-4-(2)6-difluoro-benzyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 509.1 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 44 7-Bromo-4-cyclohexyl-2-isopropyl-3-oxo-2,3)4,5-tetrahydro-benzo[f][l)4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 487.2 (M-f-23), was obtained in analogy to example 3 from cyclohexylamine, 2-(4-bromo-2-formyl-phenox7)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 45 7-Bromo-2-isopropyl-3-oxo-4-(3-trifiuoromethyl-benzyl)-2,3,4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 567.2 (M+l), was obtained in analogy to example 3 from 3-trifluoromethylbenzylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 46
4-(l-Beii2yl-piperidin-4-yl)-7-bromo-2-isopropyl-3-oxo-2)3,4,5-tetrahydxo-benzo[f] [l,4]oxazepine-5-carboxylic acidbutylamide
The title compound, MS m/e: 556.21 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 47 7>9-DicUoro-2-me1±yl-3-oxo-4-(^ tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 497.15 (M+23), was obtained in analogy to example 3 from 1,2,3,4-tetrahydro-naphthalen-l-ylamine, 2-(2,4-dicHoro-6-formyl-phenoxy)-propionic acid, and 2-isocyano-2-methyl-propane.
Example 48 7-Bromo-2-isopropyl-3-oxo-4-(l,2)3)4-tetrahydro-naphthalen-l-yl)-2,3)4,5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 535.17 (M+23), was obtained in analogy to example 3 from 1,2,3,4-tetrahydxo-naphthalen-l-ylamine, 2-(4-bromo~2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 49 7-Bromo-4-(l-carbamoyl-2-phenyl-ethyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-caxboxylic acid cyclohexylamide
The title compound, MS m/e: 556.17 (M+l), was obtained in analogy to example 3 from2~amino-3-phenyl-propionamide, 2-(4-bromo-2-formyl-phenox)0-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 50 7-Bromo-2-isopropyl-3-oxo-4-(l,2)3,4-tetrahydro-naphthalen-l-yl)-2,3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acidbutylamide
The tide compound, MS m/e: 535.17 (M+23), was obtained in analogy to example 3 from 1,2,3,4-tetrahydro-naphthalen-l-ylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.

Example 51
7-Bromo-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4?5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 474.13 (M+l), was obtained in analogy to example 3 from pyridin-3-yl-methylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 52 7-Bromo-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetraliydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 500.15 (M-fl), was obtained in analogy to example 3
from pyridin-3-yl-methylamine, 2-(4-bromo-2-formyl-phenoxy)»3-methyl-butyric acid, and isoq^ano-cyclohexane.
Example 53 7-Bromo-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3)4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 474.13 (M+l), was obtained in analogy to example 3 from pyridin-3-yl-methylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid,
and 1-isocyano-butane.
Example 54 7-Bromo-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 526.16 (M+l), was obtained in analogy to example 3 from2-(lH'indol-3-yl)-ethylamine,2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane'.
Example 55 7-Bromo-2-isopropyl-3-oxo-4-(2,2,2-trifluoro-ethyl)-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 491.11 (M+l), was obtained in analogy to example 3 from 2,2,2-trifhioroethylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 56 7-Bromo-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2,3J4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 526.16 (M+l), was obtained in analogy to example 3 from2-(lH-indol-3-yl)-ethylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 57 7-Brom.o-4-[2-(5-fluoro-lH-indol-3--yl)-l-niethyl-ethyl]-2-isopropyl-3-oxo-2)3,4)5-tetrah.ydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 580.2 (M+23), was obtained in analogy to example 3 from2-(5-fluoro-lH-indol-3-yl)-l-methyl-ethylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 58 4-Cyclohexyl-2-isopropyl-8-methoxy-3-oxo-2>3)4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 417.27 (M+l), was obtained in analogy to example 3 from cyclohexylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 59 4-(3,5-Dichloro-benzyl)-2-isopropyl-8-methoxy-3-oxo-2)3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 54L17 (M+23), was obtained in analogy to example 3 from 3,5-dichlorobenzylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 60 4-(2-Chloro-benzyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
R04The title compound, MS m/e: 485.22 (M+l), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(2-formyl-5-methox7-phenox7)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 61 4-(2,6-Difluoro-benzyl)-2-isopropyl-8-methoxy-3-oxo-2)3)4)5-tetrahydTO-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 487.23 (M+1), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(2-formyl-5-methoxy-plienoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 62 2-Isopropyl-8-methoxy-3-oxo-4-(3-trifluoromethyl-benzyl)-2>3)4?5-tetrahydro-benzoff] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e; 493.22 (M+l), was obtained in analogy to example 3 from 3-trifluoromethylbenzylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 63 4-(l-Benzyl-piperidin-4-yl)-2-isopropyl-8-methoxy-3-oxo-2,3)4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 508.31 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(2-formyl-5-meth^ acid, and 2-isocyano-2-methyl-propane.
Example 64 4-(l-Benzyl-piperidm-4-yl)-2-isopropyl-8-methoxy-3-oxo-2,3,435-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 534.33 (M-f-1), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyI-butyric acid, and isocyano-cyclohexane.
Example 65 4-(l-Benzyl-piperidin-4-yl)-2-isopropyl-8-rnethoxy-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 508.31 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(2-formyl-5-methox}?'-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.

Example 66 2--Isopropyl-8-methoxy-3-oxo-4-(l)2,3>4-tetrahydro-naphthalen-l-yl)-2?3)4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 487.27 (M+23), was obtained in analogy to example 3 from l32J354-tetrahydro-naphthalen-l-ylamine32-(2-formyl-5-methox7-phenox7)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 61 2-Isopropyl-8-methoxy-3-oxo-4-(l,2>3,4-tetrahydro-naplithalen-l-yl)-2,3)4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 513.28 (M+23), was obtained in analogy to example 3 from 1,2,3,4-tetrahydro-naphthalen-l-ylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 68 2-Isopropyl-8-methoxy-3-oxo-4-(l>2,3>4-tetrahydro-naphthalen-l-yl)-2,3J4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide .
The title compound, MS m/e: 465.27 (M+l), was obtained in analogy to example 3 from l,2,334-tetrahydro-naphthalen-l-ylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 69 2-Isopropyl-8-methoxy-3-oxo-4-pyridin-3-ylmethyl-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 426.23 (M4-1), was obtained in analogy to example 3 frompyridin-3-yl-methylamine>2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 70 4-Benzo[l,3]dioxol-5-ylmetliyl-24sopropyl-8-metlioxy-3-oxo-2>3J4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 469.23 (M+l), was obtained in analogy to example 3 frombenzo[l?3]dioxol-5-yl-methylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 71
2-Isopropyl-8-meAoxy-3-oxo-4-pyridin-3-ylmethyl-2)3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 452.25 (M+l), was obtained in analogy to example 3
frompyridin-3-yl-methylamineJ2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyri^ acid, and isocyano-cyclohexane.
Example 72 4-Benzo [ 1,3] dioxol-5-ylmethyl-2-isopropyl-8-methosy-3-oxo-2>3?4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 495.24 (M+l), was obtained in analogy to example 3 from benzo[l)3]dioxol-5-yl-methylamine)2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 73 4-[2-(lH-Indol-3-yl)-ethyl]-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The tide compound, MS m/e: 478.26 (M+l), was obtained in analogy to example 3 from2-(lH-indol-3-yl)-ethylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 74 4-[2-(lH4ndol-3-yl)-ethyl]-2-isopropyl-8-methoxy-3-oxo-2,3>4,5-te1xahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide.
The title compound, MS m/e: 504.28 (M+l), was obtained in analogy to example 3 from2-(lH-indol-3-yl)-ethylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 75 4-(2,6-Difluoro-benzyl)-2-isopropyl-3-oxo-2>3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 457.22 (M+l), was obtained in analogy to example 3 . from 2,6-difluorobenzylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 76
4-(l-Benzyi-piperidin-4-yl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 478.3 (M+l), was obtained in analogy to example 3
from l-benzyl-piperidin-4-ylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and 2-
isocyano-2-methyl-propane.
Example 77 4-(l-Benzyl-piperidin-4-yl)-2-isopropyl-3-oxo-2)3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 504.32 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 78 2-Isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3>4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 396.22 (M+l), was obtained in analogy to example 3 from pyridin-3-yl-methylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 79 2-Isopropyl-3-oxo-4-pyridin-3-ybnethyl-2)3,4,5-tetrahydro-benzo [f] [1,4] oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 422.24 (M+l), was obtained in analogy to example 3 from p)Tidm-3-yl-methylamine, 2-(2-formyl-phenoxy)-3-methyl-buiyric acid, and isocyano-cyclohexane.
Example 80 4-(3-Dimediylamino-2,2-dimethyl-propyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 444.32 (M+l), was obtained in analogy to example 3 from2,2,N',N:'-tetramethyl-propane-l,3-diamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 81
4-[2-(lH-Indol-3-yI)-ethyl]-2-isopropyl-3-oxo-2>3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 448.25 (M+l), was obtained in analogy to example 3 from 2-(lH-indol-3-yl)-ethylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl~propane.
Example 82 4-[2-(lH-Indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2>3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 448.25 (M+l), was obtained in analogy to example 3 from 2-(lH-indol-3-yl)-ethylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 83 2-Isopropyl-4-[2-(5-methoxy-lH-indol-3-yl)-ethyl]-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 478.26 (M+l), was obtained in analogy to example 3 from2-(5-methox)^-lH-indol-3-yl)-ethylamine)2-(2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 84 2-Isopropyl-4-[2-(5-metiLOxy-lH-indol-3-yl)-ethyl]-3-oxo-2,3J4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 504.28 (M+l), was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)-ethylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 85 7-Chloro-4-(2-chloro-benzyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 489.16 (M+l), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 86
7-CHoro-2-isopropyl-3-oxo-4-(l?2>3J4-tetrahydro-naphthalen-l-yl)-2J3)4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamid
The title compound, MS m/e: 517.3943 (M+23), was obtained in analogy to example 3 from 1,2,3,4-tetxahydro-naphthalen-l-ylamine, 2-(4-cHoro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
t. Example 87
4-(2-Benzylsialfanyl-ethyl)-7-chloro-2-isopropyl-3-oxo-2,3,455-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The tide compound, MS m/e: 537.2 (M+23), was obtained in analogy to example 3 from 2-benzylsulfanyl-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 88 7-Chloro-2-isopropyl-3-oxo-4-pyridin-3-ylinethyl-2,3J4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 430.18 (M-f 1), was obtained in analogy to example 3 from pyxidin-3-yl-methylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 89 7-CUoro-2-isopropyl-3-oxo-4-pyridm-3-ylmethyl-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 456.2 (M+l), was obtained in analogy to example 3 from pyridin-3-yl-methylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 90 7-Chloro-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2>3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 430.18 (M+l), was obtained in analogy to. example 3 from pyridin-3-yl-methylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.

Example 91 7-CHLoro-4-(3-die1±Lylaiiiino-propyl)-2-isopropyl-3-oxo-2>3)4)5-tetxahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 478.28 (M+l), was obtained in analogy to example 3 from N\N'-diethyl-propane-l,3-diamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid , and isocyano-cyclohexane.
Example 92 7-CUoro-24sopropyl-4-[2-(5-metlioxy-lH-indol-3-yl)'ethyl]-3-oxo-2,3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 538.24 (M+l), was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3~ methyl-butyric acid, and isocyano-cyclohexane.
Example 93
4-(4-Chloro-2-fluoro-benzyl)-7-methoxy-3-oxo-2-phenyl-2)3)4,5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 511.17 (M+l), was obtained in analogy to example 3 from 4-chloro-2-fluorobenzylamine, (2-formyl-4-methoxy-phenoxy)-phenyl-acetic acid, and 2-isocyano-2-methyl-propane.
Example 94
i 7-Chloro-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 482.21 (M+l), was obtained in analogy to example 3 from2-(lH-indol-3-yl)-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
5 Example 95
7-CHoro-2-isopropyl-4-[2-(5-methoxy-lH-indol-3-yl)-ethyl]-3-oxo-2,3,4,5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 512.22 (M+l), was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)'ethylamine, 2-(4-cHoro-2-formyl-phenoxy)-3~ iO methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 96 7-Chloro-4-(4-chloro-2-fluoro-benzyl)-2-isopropyl-3-oxo-2J3)4>5-tetrahydro-3enzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 507.15 (M+l), was obtained in analogy to example 3 from4-chloro-2-fluorobenzylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 97 7)9-Dichloro-4-(4-chloro-2-fluoro-benzyl)-2-methyl-3-oxo-2,3)4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 513.08 (M+l), was obtained in analogy to example 3 from 4-chloro-2-fluorobenzylamine, 2-(2,4-dichloro-6-formyl-phenoxyr)-propionic acid, and isocyano-cyclohexane.
Example 98 4-(9H-Fluoren-9-yl)-7-methoxy-2-methyl-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 497.24 (M+l), was obtained in analogy to example 3 from 9H-fluoren-9-ylamine, 2-(2-formyl-4-methoxy-phenoxy)-propionic acid, and isocyano-cyclohexane.
Example 99 4-(3,5-Dichloro-benzyl)-8-dietiiylainino-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 534.22 (M+l), was obtained in analogy to example 3 from 3,5-dichlorobenzylainine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 100 4-(3,5-Dichloro-benzyl)-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 560.24 (M+l), was obtained in analogy to example 3 from 3,5-dichlorobenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 101 8-Dietiiylainino-2-isopropyl-3-oxo-4-(3-trifluoroinetiiyl-benzyl)-273)4)5-teti:ahydro-benzo[f] [l>4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 560.3 (M+l), was obtained in analogy to example 3 from3-trifluoromet3aylbenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 102 8-Diethylamino-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2>3)4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 545.34 (M+l), was obtained in analogy to example 3 from2-(lH-indol-3-yl)-ethylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 103 4-(4-DimeAylamino-benzyl)-2-isopropyl-8-methoxy-3-oxo-2,3>4J5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 494.29 (M+l), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 104 4-(2-CMoro-benzyl)-8-dietiiylaniino-2-isopropyl-3-oxo--2,3)4,5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 500.3 (M+l), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 105 8-Diethylaniiiio~4-(2,6-difluoro-benzyl)-2-isopropyl-3-oxo-2>3>4,5-tetrahydro--benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 502.3 (M+l), was obtained in analog)7 to example 3 from 2,6-difluoroben2ylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 106 4-(2-CUoro-benzyl)-8-dietliylamijDO-2-isopropyl-3-oxo-2?3>4)5-tetrahydro-benzoffJfl^oxazepine-S-carboxylic acid cyclohexylamide
The title compound, MS m/e: 526.4 (M+1), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 107 8-Diethylamino-4-(2,6-difluoro-benzyl)-2-isopropyl-3-oxo-2)3,4,5-tetrahydro-benzo[f] [l>4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 528.4 (M+l), was obtained in analogy to example 3 from 2,6-difl.uorobenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 108 4-(2-CUoro-ben27l)-8-diethylamino-2-isopropyl-3-oxo-2>3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 500.4 (M+l), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-but)T:ic acid, and 1-isocyano-butane.
Example 109 8-Diethylamino-4-(2,6-difluoro-benzyl)-2-isopropyl-3-oxo-2?3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 502.4 (M+l), was obtained in analogy to example 3 from2,6-difluorobenzylamine,2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric
acid, and 1-isocyano-butane.
Example 110 4-Cyclohexyl-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 458.4 (M+l), was obtained in analogy to example 3 from cyclohexylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 111
8-Dietfaylamino-2-isopropyl-3-oxo-4-(3-trifluoroniethyl-benzyl)-2,354>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 534.4 (M+l), was obtained in analogy to example 3 from 3-trifluoromethylbenzylamine, 2-(5-diethylamino-2-formyl-phenox)0-3-methyl-but)T:ic acid, and 2-isocyano-2-methyl-propane.
Example 112 8-Diethylamino-2-isopropyl-3-oxo-4-(3-trifluoronietliyl-benzyl)-273)4J5-tetrahydro-benzo[f] [1,4] oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 534.4 (M+l), was obtained in analogy to example 3 from 3-trifluoromethylbenzylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane,
Example 113 4-(l-Benzyl-piperidin-4-yl)-8-diethylamino-2-isopropyl-3-oxo-2,3>435-tetrahydro-benzo [f] [ 1,4] oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 549.4 (M+l), was obtained in analogy to example 3 from 1-benzyl-piperidin-4-ylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 114 ) 8-Diethylamino-2-isopropyl-3-oxo-4-(l,2,3)4-tetrahydro-naphthalen-l-yl)-2,3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 506.4 (M+l), was obtained in analogy to example 3 from 1,2,3,4-tetrahydro-naphthalen-l-ylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
5 Example 115
8-Dietiiylamino-2-isopropyl-3-oxo-4-(l,2,3)4-tetrahydro-naphthalen-l-yl)-2>3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 532.4 (M+l), was obtained in analogy to example 3 from 1,2,3,4-tetrahydro-naphthalen-l-ylamine, 2-(5-diethylamino-2-formyl-phenoxy)-0 3-methyl-butyric acid, and isocyano-cyclohexane.

Example 116 8-Diethylamino-2-isopropyl-3-oxo-4-(l,2,3,4-tefr tetxahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 506.4 (M+l), was obtained in analogy to example 3 from 1,2,3,4-tetrahydro-naphthalen-l-ylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 117 4-Benzo[l,3]dioxol-5-ylme&yl-8-dietliylammo-2-isopropyl-3-oxo-2,3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 510.4 (M+l), was obtained in analogy to example 3 frombenzo[l,3]dioxol-5-yl-methylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 118 4-Benzo[l,3]dioxol-5-ylmethyl-8-diethyta^ benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 536.4 (M+l), was obtained in analogy to example 3 from benzo[ 1,3]dioxol-5-yl-methylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 119 4-Benzo[l,3]dioxol-5-ylmethyl-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 510,4 (M+l), was obtained in analogy to example 3 from benzo[ 1,3] dioxol-5-yl-methylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 120 8-Diethylamino-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2,3)4>5-tetrahydxo-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 519.4 (M+l), was obtained in analogy to example 3 from 2-(lH-indol-3-yl)-ethylamine, 2-(5-diethylamino-2-formyl-phenox7)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 121 8-Diethylammo-24sopropyL tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 549.4 (M+l), was obtained in analogy to example 3
from2-(5-methoxy-lH-indol-3-yl)-ethyk^
3-methyl-butyric acid, and 1-isocyano-butane.
Example 122 4-(4-Dimethylamino-benzyl)-2-isopropyl-8-methoxy-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 468.4 (M+l), was obtained in analogy to example 3
from 4-dimethylaminobenzylamine, 2-(2-formyl-5-methox7-phenoxy)-3-methyl-butyric
acid, and 1-isocyano-butane.
Example 123 4-(4-Chloro-2-fluoro-benzyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydro-> benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 477.2 (M+l), was obtained in analogy to example 3 from 4-chloro-2-fluorobenzylamine, 2-(2-formyl-5-methoxy-phenoxy)~3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 124 3 4-(4-Chloro-2-fluoro-benzyl)-2-isopropyl~8-methoxy-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 503.3 (M+l), was obtained in analogy to example 3 from 4~chloro-2-fiuorobenzylamine, 2-(2-formyl-5-methoxy-phenox)0-3-methyl-butyric acid, and isocyano-cyclohexane.
5 Example 125
4-(4-Chloro-2-fluoro-benzyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydxo-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 477.3 (M+l), was obtained in analogy to example 3 from 4-chloro-2-fluorobenzylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl--0 butyric acid, and 1-isocyano-butane.

Example 126 7-Bromo-4-(2,6-difluoro-benzyl)-2-methyl-3-oxo-2,3)4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 529.2 (M+23), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(4-bromo-2-formyl-phenoxy)-propionic acid, and isocyano-cyclohexane.
Example 127 {[4-(l-Benzyl-piperidin-4-yl)-2-isopropyl-3-oxo-2>3>4,5-tetrahydro-benzo[fj [l,4]oxazepine-5-carbonyl]-amino}-acetic acidtert-butyl ester
The title compound, MS m/e: 536.4 (M+1), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 128 ({7-CWoro-2-isopropyl-4-[2-(5-methoxy-lH-indol-3-yl)-ethyl]-3-oxo-2>3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl}-amino)-acetic acid tert-butyl ester
The title compound, MS m/e: 592.2 (M+23), was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)-ethylamine, 2-(4-cHoro-2-formyl-phenoxy)-3-methyl-butyric acid, and ilsocyano-acetic acid tert-butyl ester.
Example 129
({7-Chloro-2-isopropyl-4-[2-(4-nitro-phenyl)-ethyl]-3-oxo-2,3,4,5-tetrahydro-benzo[f] [1,4] oxazepine-5-carbonyl}-amino)-acetic acid tert-butyl ester
The title compound, MS m/e: 546.2 (M+l), was obtained in analogy to example 3 from 4-nitrophenylethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
5 Example 130
4-(lH-Benzoimidazol-2-ylnie1hyl)-9-ethoxy-2-isopropyl-3-oxo-2,3)4,5-tetrahydro-benzo[f] [l^joxazepine-S-carboxylic acid tert-butylamide
The title compound, MS m/e: 479.3 (M+l), was obtained in analogy to example 3 frombenzoimidazol-2-yl-methylamine, 2-(2-ethoxy-6-formyl-phenox7)-3-methyl-0 butyric acid, and 2-isocyano-2-methyl-propane.

Example 131
4-(lH-Benzoimidazol-2-ylmethyl)-9-e1±ioxy-2-isopropyl-3-oxo-2J3>4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The tide compound, MS m/e: 505.3 (M-f 1), was obtained in analogy to example 3 frombenzoirrndazol-2-yl-methylamine, 2-(2-ethoxy-6-formyl-phenoxy)-3-methyl-butyric acid, andisocyano-cyclohexane.
Example 132 7-Chloro-4-(2,6-difl.uoro-benzyl)-2-isopropyl-3-oxo-2,3>4>5-tetraliydro-benzo [f] [1,4] oxazepine-5-carboxylic acid benzylamide
The tide compound, MS m/e: 499.2 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyanomethyl-benzene.
Example 133 7-Chloro-4-cyclohexyl-2-isopropyl-3-oxo-2>3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid benzylamide
The tide compound, MS m/e: 455.3 (M+l), was obtained in analogy to example 3 from cyclohexylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyanomethyl-benzene.
Example 134 {[7-Chloro-2-isopropyl-3-oxo-4-(3-trifluoromethyl-benzyl)-2,3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The tide compound, MS m/e: 577.18 (M+23), was obtained in analogy to example 3 from 3-trifluoromethylbenzylamine, 2-(4-chloro-2-formyl-phenox7)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 135 4-(l-Benzyl-piperidin-4-yl)-2-isopropyl-3-oxo-2)3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid benzylamide
The tide compound, MS m/e: 512.4 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and isocyanomethyl-benzene.

Example 136 4-(l-Benzyl-piperidin-4-yl)-7-chloro-2-isopropyl-3-oxo-2?3)4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acidbenzylamide
The title compound, MS m/e: 546.3 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyanomethyl-benzene.
Example 137 {[4-(l-Benzyl-piperidin-4-yl)-7-chloro-2-isopropyl-3-oxo-2,3>4>5-tetrahydro-benzo[fj [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The title compound, MS m/e: 570.3 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 138 {[4-(l-Carbamoyl-2-phenyl-ethyl)-7-chloro-2-isopropyl-3-oxo-2>3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The title compound, MS m/e: 566.21 (M+23), was obtained in analogy to example 3 from2-amino-3-phenyl-propionamide, 2-(4-cHoro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 139 7-Chloro-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2>3>4J5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid benzylamide
The title compound, MS m/e: 516.3 (M+l), was obtained in analogy to example 3 from2-(lH-indol-3-yl)-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyanomethyl-benzene.
; Example 140
7-CMoro-4-(4-diine1±Lylamino-benzyl)-2-isopropyl-3-oxo-2J3,4>5-tetrahydxo-benzo[f] [l,4]oxazepine-5-carboxylic acidbenzylamide
The tide compound, MS m/e: 528.3 (M+23), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric ) acid, and isocyanomethyl-benzene.

Example 141 {[4-(2-Benzylsxilfanyl-ethyl)-7-chloro-2-isopropyl-3-oxo-2,3,4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The title compound, MS m/e: 569.3 (M+23)0 was obtained in analogy to example 3 from 2-benzylsulfanyl-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 142 {[7-CMoro-24sopropyl-4-(2-methylsulfanyl-ethyl)-3-oxo-2,3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The tide compound, MS m/e: 493.3 (M+23), was obtained in analogy to example 3 from 2-methylsulfanyl-ethylamine, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 143 {[7-Chloro-2-isopropyl-3-oxo-4-(4-sulfamoyl-benzyl)-2,3>4,5-tetraliydro-benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The title compound, MS m/e: 588.3 (M+23), was obtained in analogy to example 3 from4-aminomethyl-benzenesulfonamide, 2-(4-chloro-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 144 ({2-Isopropyl-4-[2-(5-mtro-pyridin-2-ylamino)-ethyl]-3-oxo-2,3?4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl}-amino)-acetic acid tert-butyl ester
The title compound, MS m/e: 528.3 (M+l), was obtained in analogy to example 3 from2-(5-nitro-pyridin-2-ylamino)-ethylamine, 2-(2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 145 4-(2,6-Difluoro-benzyl)-9-ethoxy-2-isopropyl-3-oxo-2)3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 501.3 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(2-ethoxy-6-formyl-phenox)0-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 146
4-(4-Dimethylamino-benzyl)-9-ethoxy-2-isopropyl-3-oxo-2>3)4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 482.4 (M+l), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(2-ethoxy-6-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 147 4-(l-Benzyl-piperidin-4-yl)-9-ethoxy-2-isopropyl-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 548.4 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(2-ethoxy-6-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 148 4-(4-Dimethylamino-benz)d)-9-ethoxy-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-bcnzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 529.4 (M+23), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(2-ethoxy-6-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 149 9-Edioxy-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2,3}4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 518.4 (M+l), was obtained in analogy to example 3
from2-(lH-indol-3-yl)-ethylam
acid, and isocyano-cyclohexane.
Example 150 9-Ethoxy-2-isopropyl-4-[2-(5-metkoxy-l^ benzo[f] [l,4]oxazepine-5~carboxylic acid tert-butylamide
The title compound, MS m/e: 522.4 (M+l), was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)-ethylamine, 2-(2-ethoxy-6-formyl-phenoxy)-3-> methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 151 9-Ethoxy-2-isopropyl-4-[2-(5-^^ benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 548.4 (M+l)> was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)-etiylamine)2-(2-ethoxy-6-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 152 7-Bromo-4-(2-chloro-benzyl)-2-isopropyl-3-oxo-2,334,5-tetraliydro-benzo[f][l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 555.2 (M+l), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-l53-dimethyl-benzene.
Example 153 7-Bromo-4-cyclohexyl-2-isopropyl-3-oxo-2>3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 513.2 (M+l), was obtained in analogy to example 3 from cyclohexylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-l,3-dimethyl-benzene.
Example 154 7-Bromo-2-isopropyl-3-oxo-4-(2-thiophen-2-yl-ethyl)-2,3)4>5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 541.2 (M+l), was obtained in analogy to example 3 from 2-thiophen-2-yl-ethylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-but)o:ic acid, and 2-isocyano-l,3-dimethyl-benzene.
Example 155 4-(l-Benzyl-piperidin-4-yl)»7-bromo-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 604.3 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylaniine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-l,3-dimethyl-benzene.

Example 156 7-Bromo-2-isopropyl-3-oxo-4-p}Tidin-3-ylmethyl-2,3>4,5-tetxajbydro-benzo[f][l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 522.2 (M-fl), was obtained in analogy to example 3 from pyridin-3-yl-methylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-l>3-dimethyl-benzene.
Example 157 7-Bromo-4-carbamoylmethyl-24sopropyl-3-oxo-2)3,4,5-tetrahydro-benzo[f] [l^joxazepine-S-carboxylic acid tert-butylamide
The title compound, MS m/e: 440.2 (M+l), was obtained in analogy to example 3
from 2-amino-acetamide, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-
isocyano-2-methyl-propane.
Example 158 7-Bromo-4-fuxan-2-ylinethyl-2-isopropyl-3-oxo-2>3)4>5-tetrahydxo-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 485.1 (M+23), was obtained in analogy to example 3 from C-furan-2-yl-methylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 159
7-Bromo-2-isopropyl-3-oxo-4r(2-phenyl-cyclopropyl)-2,354,5-tetrahydro-benzo[f][l54]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 525.2 (M-f-l)> was obtained in analogy to example 3
from2-phenyl-cyclopropylamine,2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 160 7-Bromo-4-(4-dim.etliylainino-benzyl)-2-isopropyl-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 538,3 (M+23), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.

Example 161
7-Bromo-4-(4-dimethylainino-benzyl)-2-isopropyl-3-oxo-2)3>4>5-tetxah.ydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 516.3 (M+l), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 162 4-(2-Benzylsxilfanyl-ethyl)-7-bromo-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 559.2 (M+l), was obtained in analogy to example 3 from 2-benzylsulfanyl-ethylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 163 7-Bromo-2-isopropyl-4-(2-metliylsulfanyl-ethyl)-3-oxo-2>3)4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxy!ic acid cyclohexylamide
The title compound, MS m/e: 483.2 (M+l), was obtained in analogy to example 3 from 2-methylsulfanyl-ethylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-q^clohexane.
Example 164 7-Bromo-2-isopropyl-4-[2-(4-nitro-phenyl)-ethyl]-3-oxo-2,3)4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 558.3 (M+l), was obtained in analogy to example 3 from 4-nitrophenylethylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 165 7-Bromo-4-(4-chloro-2-fluoro-benzyl)-2-isopropyl-3-oxo-2,3,4>5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid cyclohexylamid
The title compound, MS m/e: 551.2 (M+l), was obtained in analogy to example 3 from 4-cHoro-2-fluorobenzylamine, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 166 7-Bromo-4-(4-dimethylamino-benzyl)-2-isopropyl-3-oxo-2,3)4)5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 564.3 (M+23), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(4-bromo-2-formyl-phenox7)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 167 7-Bromo-2-isopropyl-3-oxo-4-(2-oxo-tetrahydro-furan-3-yl)-2J3,4,5-tetrahydxo-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 493.2 (M+1), was obtained in analogy to example 3 from 3-amino-dihydro-furan-2-one, 2-(4-bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 168 7-Bromo-2-isopropyl-4-[2-(5-nitro-p}rridin-2-ylainino)-ethyl]-3-oxo-2,3,4)5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 574.2 (M+l), was obtained in analogy to example 3 from2-(5-nitro-pyridin-2-ylamino)-ethylamine, 2-(4~bromo-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 169 {[7-Bromo-4-(4-chloro-2-fl.uoro-benzyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydro-benzo[f] [ 1,4] oxazepine-5-carbonyl]-amino}--acetic acid tert-butyl ester
The title compound, MS m/e: 635.1 (M+23), was obtained in analogy to example 3 from 4-chloro-2-fluorobenzylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 170 7-Bromo-24sopropyl-9-methoxy-4-[2-(5-methoxy^ tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 634.3 (M+l), was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)-ethylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-l,3-dimethyl-benzene.

Example 171 7-Bromo-2-isopropyl-9-methoxy-4-[2-(^
2,3,4,5-tetrahydro-benzoff] [l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 626.3 (M+l), was obtained in analogy to example 3 from 2-(5-nitro-pyridin-2-ylamino)-ethylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-l,3-dimethyl-benzene.
Example 172 4-(4-Dimetiiylamino-benzyl)-2-isopropyl-8-metlioxy-3-oxo-2?3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid benzylamide
The title compound, MS m/e: 502.4 (M+l), was obtained in analogy to example 3
from 4-dimethylaminobenzylamine, 2-(2-formyl-4-methoxy-phenoxy)-3-methyl-butyTic
acid, and isocyanomethyl-benzene.
Example 173 4-(4-Dimethylamino-benzyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 515.4 (M+l), was obtained in analogy to example 3
from 4-dimethylaminobenzylamine, 2-(2-formyl-4-methoxy-phenoxy)-3-methyl-butyric
acid, and 2-isocyano-l,3-dimethyl-benzene.
Example 174 2-tert-Butoxyinethyl-7-chloro-4-(2,6-difluoro-benzyl)-3--oxo-2J3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 557.21 (M+23), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 3-tert-butoxy-2-(4-chloro-2-formyl-phenoxy)-propiQnic acid, andisocyano-cyclohexane.
Example 175 2-tert-Butoxymelhyl-7-cUoro-4-fuxan-2-ylinethyl-3-oxo-2,3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 511.2 (M+23), was obtained in analogy to example 3 from furan-2-yl-methylamine, 3-tert-butoxy-2-(4-chloro-2-formyl-phenoxy)-propionic acid, and isocyano-cyclohexane.

Example 176 7-Bromo-4-(2,6-difluoro-benzyl)-2-isopropyl-9-methoxy-3-oxo-2>3)4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 565.2 (M+l), was obtained in analogy to example 3 from 2,6-difluorobenzylamine, 2-(4-bromo-2-formyl-6-methoxy-phenox7)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 177 4-(l-Benzyl-piperidin-4-yl)-7-bromo-2-isopropyl-9-methoxy-3-oxo-2>3>4)5-tetrahydro-benzo[fj [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 586.3 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(4-bromo-2-formyl-6-methoxyr-phenoxy)-3-methyl-butyric acid, and 2-isocyano-2-methyl-propane.
Example 178 7-Bromo-4-(4-dimetiiylaniino-benzyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4?5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 594.3 (M-f 23), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, arid isocyano-cyclohexane.
Example 179 4-(l-Benzyl-piperidin-4-yl)-7-bromo-2-isopropyl-9-methoxy-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxyiic acid butylamide
The title compound, MS m/e: 586.3 (M+l), was obtained in analogy to example 3 from l-benzyl-piperidin-4-ylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and 1-isocyano-butane.
Example 180 7-Bromo-4-(4-dimethylamino-benzyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide
The title compound, MS m/e: 568.3 (M+23), was obtained in analogy to example 3 from 4-dimethylaminobenzylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy")-3-methyl-butyric acid, and 1-isocyano-butane.

Example 181 7-Bromo-2-isopropyl-9-methoxy-3-oxo-4-pyridin^^ benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS xn/e: 530.3 (M+l), was obtained in analogy to example 3 frompyridin-3-yl-methylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.
Example 182 7-Bromo-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-9-methoxy-3-oxo-2,3,4J5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 556.3 (M+l), was obtained in analogy to example 3 from2-(lH-indol-3-yl)-ethylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid> and 2-isocyano-2-methyl-propane.
Example 183 7-Bromo-24sopropyl-9-methoxy-4-[2-(5-metiiox7-lH-indol-3-yl)-ethyl]-3-oxo-2,3>4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide
The title compound, MS m/e: 586.3 (M+l), was obtained in analogy to example 3 from 2-(5-methoxy-lH-indol-3-yl)-ethylamine> 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyxic acid, and 2-isocyano~2-methyl-propane.
Example 184 7-Bromo-24sopropyl-9-methoxy-4-[2-(5-metlioxy-lH-indol-3-yl)-ethyl]-3-oxo-2>3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 612.3 (M+l), was obtained in analogy to example 3 from2-(5-methoxy-lH-indol-3-yl)-ethylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexarie.
Example 185 7-Bromo-2-isopropyl-9-metlioxy-4-[2-(5-ni1xo-pyTidin-2-ylamino)-ethyl]-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid cyclohexylamide
The title compound, MS m/e: 604.3 (M+l), was obtained in analogy to example 3 from 2-(5-nitro-pyridin-2-ylamino)-ethylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-cyclohexane.

Example 186
{[7-Bromo-4-(2-chloro-benzyl)-2-isopropyl-9-metboxy-3-oxo-2?3J4)5-tetrahydro-benzoff] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The title compound, MS m/e: 617.2 (M+23), was obtained in analogy to example 3 from 2-chlorobenzylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 187 [(7-Bromo-4-carbamoylmethyl-2-isopropyl-9-methoxy-3-oxo-2?3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl)-amino]-acetic acid tert-butyl ester
The title compound, MS m/e: 550.2 (M+23), was obtained in analogy to example 3 from 2-amino-acetamide, 2-(4-bromo-2-formyl-6-methoxy-phenox)0-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 188
{[7-Bromo-4-(3,5-dichloro-benzyl)-2-isopropyl-9-methoxy-3-oxo-2,3>4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The title compound, MS m/e: 651.07 (M+23), was obtained in analogy to example 3 from 3,5-dichlorobenzylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 189 (
{[7-Bromo-2-isopropyl-9-methoxy-3-oxo-4-(2-phenyl-cyclopropyl)-2?3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester
The title compound, MS m/e: 587.2 (M+l), was obtained in analogy to example 3 from 2-phenyl-cyclopropylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isoq^ano-acetic acid tert-butyl ester.
Example 190 {[7-Bromo-2-isopropyl-9-methoxy-3-oxo-4-(l,2,3,4-tetrahydro-naphthalen-l-yl)-2,3,4,5-tetrahydro-benzoff] [1,4] oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester

The title compound, MS m/e: 623.3 (M-h23), was obtained in analogy to example 3 from l>2,3,4-tetrahydro-naphthalen-l-ylamine, 2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 191 [(7-Bromo-2-isopropyl-9-metlioxy-3-oxo-4-pyri^ benzo[f] [l,4]oxazepine-5-carbonyl)-amino]-acetic acid tert-butyl ester
The title compound, MS m/e: 562.2 (M+l), was obtained in analogy to example 3 from pyridin-3-yl-metiiylamine,2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 192 [(4-Benzo[l,3]dioxol-5-yknethyl-7-bromo-2-isopropyl-9-methoxy-3-oxo-2,3,4>5-tetrahydro-benzo[f] [l,4]oxazepine-5-carbonyl)-amino]-acetic acid tert-butyl ester
The title compound, MS m/e: 627.3 (M+23), was obtained in analogy to example 3 from benzo[l,3]dioxol-5-yl-methylamine,2-(4-bromo-2-formyl-6-methoxy-phenoxy)-3-methyl-butyric acid, and isocyano-acetic acid tert-butyl ester.
Example 193 9-Ethoxy-4-[2-(lH-indol-3-yl)-ethyl]-2-isopropyl-3-oxo-2J3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid (2,6-dimethyl-phenyl)-amide
The tide compound, MS m/e: 540.4 (M-f 1), was obtained in analogy to example 3 from 2-(lH-indol-3-yl)-ethylamine, 2-(2-ethoxy-6-formyl-phenoxy)-3-metbyl-butyric acid, and2-isocyano-l,3-dimethyl-benzene.
Example 194 8-Dietiiylamino-2-isopropyl-4-(l-naphthalen-l-yl-ethyl)-3-oxo-2>3)4>5-tetrahydro-benzo [fj [1,4] oxazepine-5-carboxylic acid benzylamide
The title compound, MS m/e: 564.4 (M-f 1), was obtained in analogy to example 3 from 1-naphthalen-l-yl-ethylamine, 2-(5-diethylamino-2-formyl-phenoxy)-3-methyl-butyric acid, and isocyanornethyl-benzene.
Example 195 8-Dietiiylamino-4-furan-2-ylmethyl-2-isopropyl-3-oxo-2,3>4,5-tetraliydro-benzo[f] [l,4]oxazepine-5-carboxylic acid benzylamide

The title compound, MS m/e: 490.4 (M+l), was obtained in analogy to example 3 from C-furan-2-yl-methylamine, 2-(5-diethylamino-2-formyl-plienox7)-3-methyl-butyric acid, and isocyanomethyl-benzene.
Example 196 2-Isopropyl-8-methoxy-4-(l-naphtiialen-l-yl-eliyl)-3-oxo-2>3,4,5-te1xahydro-benzo[f][l,4]oxazepine-5~carboxylic acid (2,6-dimethyl-phenyl)-amide
The title compound, MS m/e: 559.3 (M+23), was obtained in analogy to example 3 from 1-naphthalen-l-yl-ethylamine, 2-(2-formyl-5-methoxy-phenoxy)-3-methyl-butyric acid, and 2-isocyano-l,3-dimethyl-benzene.

i


Claims 1. Compounds of the general formula

wherein
R1 is hydrogen, C1-6-leweF alkoxy, halogen or -NR'R"; n is 1 or 2; R5,R" are independently from each other hydrogen or Cms-lower alkyl;
R is hydrogen, Ci.6-lowcr alkyl, -(CH2)m- C3_7-cycloalkyl, -(CH2)m-phenyl or
—(-CH^-)m-0—CM4ew#F-alkyl;
m is 0,1 or 2;
R3 is Curlewe* alkyl, -(CH2)m-C(0)0- Ci.64ewe^alkyl, C3.7-cycloalkyl or -(CH2)m-phenyl, which is unsusbtituted or substituted by one or two substituents, selected from the group consisting of halogen or Ci.$-lewefr alkyl;
R4 is -(CH2)0-phenyl, which is unsusbtituted or substituted by one or two substituents, selected from the group consisting of halogen, trifluoromethyl, -NR'R", nitro or -S02NH2, or is
- C3-rcycloalkyl, unsubstituted or substituted by phenyl, or is
- (CR'R'^o-heterocyclyl, selected from the group consisting of tetrahydropyran-4-yl, pyridin-3-yl, indol-3-yl, optionally substituted by halogen or Q-6-lower-alkoxy, or thiophen-2-yl, furan-2-yl, -NH-pyridin-2-yl, optionally substituted by nitro, or



Compounds in accordance with claim 2, wherein R3 is C3-7-cycloalkyl and R4 is tetrahydro-pyran-4-yl
6. Compounds in accordance with claim 5, which compound is 7-chloro-2-ethyl-3-oxo-4-(tetrahydro-pyran-4-yl)-2>3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide.
7. Compounds in accordance with claim 2, wherein R is C3.7-cycloalkyi and R is tetrahydro-naphthalen-1-yl.
8. Compounds in accordance with claim 7, which compounds are 7-chloro-2-isopropyl-3-oxo-4-(lJ2,3,4-tetrahydro-naphthalen-l-yl)-2J3»4)5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamid or
8-diethylamino-2-isopropyl-3-oxo-4-(l,233,4-tetrahydro-naphthalen-l-yl)-2>3J4}5-tetrahydro-benzo[f] [ l,4]oxazepine-5-carboxylic acid cyclohexylamide,
9. Compounds in accordance with claim 2, wherein R3 is C3.7-cycloalkyl and R4 is
-(CH2)0-pyridin-3-yl.
1.0. -Compounds-in-accordance with claim 9, which compound is 7-chloro-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4)5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid cyclohexylamide.
11. Compounds in accordance with claim 2, wherein R3 is lower alkyl and R is -(CH2)0-phenyl, substituted by di-halogen or NR'R".
12. Compounds in accordance with claim 11, which compounds are 7-chloro-4-(2J6-difluoro-benzyl)-2-ethyl-3-oxo-2,3)4,5-tetrahydro-benzo[f][lJ4]oxazepine-5-carboxylic acid tert-butylamide,
4-(4-dimethylamino-benzyl)-2-isoprpyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]oxazepine-5-carboxylic acid butylamide,
7-chloro-4-(4-dimethylamino-benzyl)-2-isopropyl-3-oxo-2,3,4J5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide, 4-(4-dimethylamino-benzyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydro-

benzo[f] [l,4]oxazepine-5-carboxylic acid butylamide or 7-bromo-4-(4-dimethylamino-benzyl)-2-isopropyi-3-ox;o-2J3)455-tetxahydro-benzo[f][l,4]oxazepine-5-carboxylic acid tert-butylamide.
13. Compounds in accordance with claim 2, wherein R3 is Q-6-lower alkyl and R4 is -(CR'R'^oindol-S-yl, substituted by C-1-6 lower alkoxy.
14. Compounds in accordance with claim 13, which compound is 9-ethoxy-2-isopropyl-4-[2-(5-methoxy-lH-indol-3-yl)-ethyl]-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l,4]oxazepine-5-carboxylic acid tert-butylamide.
15. Compounds in accordance with claim 2, wherein R3 is Q^-lower alkyl and R4 is C3.7-cycloalkyl.
16. Compounds in accordance with claim 13, which compound is 7-chloro-4-cyclopentyl-2-ethyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][l,4]oxazepine-5-carboxylic acid tert-butylamide.
17. Compounds in accordance with claim 2, wherein R is Ci-6-lower alkyl and R4 is
- (CH2)0-benzo[l,3]dioxol-5-yl.
18. Compounds in accordance with claim 17, which compound is 4-benzo[l,3]dioxol-5-ylmethyl-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f] [l»4]oxazepine-5-carboxylic acid tert-butylamide.
19. Compounds in accordance with claim 2, wherein R is Q-6-lower alkyl and R is 1 -benzyl-piperidin-4-yl.
20. Compounds in accordance with claim 19, which compound is

4-(l-benzyl-piperidin-4-yl)-2-isopropyl-3-oxo-2)3,4,5-tetrahydro-benzo[f][l>4]oxazepine-5-carboxylic acid tert-butylamide.
21.-Compounds in accar-dance~withuclairix2, whereinJR is -(CH2)m-phenyLandJL is C3-7-
..cycloalkyl.
22, Compounds in accordance with claim 21, which compound is 7-chloro-4-cyclohexyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][l>4]oxazepine-5-carboxylic acid benzylamide.
23. Compounds in accordance with claim 2, wherein R3 is -(CH2)m-C(0)0- Q.6- lower alkyl and R4 is -(CH2)0-phenyl, substituted by CF3 or halogen.
24. Compounds in accordance with claim 23, which compounds are
{[7-chloro-2-isopropyl-3-oxo-4-(3-trifluoromethyl-benzyl)-2,3,4,5-tetrahydro-benzo[f] [1,4] oxazepine-5-carbonyl] -amino}-acetic acid tert-butyl ester or {[7-bromo^(2_-cMorojte benzo[f] [l,4]oxazepine-5-carbonyl]-amino}-acetic acid tert-butyl ester.
25. A process for preparing a compound of formula I as defined in claim 1, which process comprises
a) reacting a compound of formula with a compound of formula

and with a compound of formula
R3NC IV to a compound of formula

wherein the substituents are as defined in claim 1, and
if desired, converting the compounds obtained into pharmaceutically acceptable acid
addition salts.
26. A compound according to any on of claims 1—24, whenever prepared by a process as claimed in claim 25 or by an equivalent method.
^27. A medicament containing one or more compounds as claimed in any one of claims 1-24 and pharmaceutically acceptable excipients.
27. A medicament according to claim 27 for the treatment of Alzheimer's disease.
The use of a compound in any one of claims 1-24 for the manufacture of medicaments for the treatment of Alzheimer's disease.


Documents:

3051-CHENP-2005 CLAIMS.pdf

3051-CHENP-2005 CORRESPONDENCE OTHERS.pdf

3051-CHENP-2005 CORRESPONDENCE PO.pdf

3051-CHENP-2005 FORM-1.pdf

3051-CHENP-2005 FORM-2.pdf

3051-CHENP-2005 FORM-3.pdf

3051-CHENP-2005 PETITIONS.pdf

3051-chenp-2005-abstract.pdf

3051-chenp-2005-claims.pdf

3051-chenp-2005-correspondnece-others.pdf

3051-chenp-2005-description(complete).pdf

3051-chenp-2005-form 1.pdf

3051-chenp-2005-form 18.pdf

3051-chenp-2005-form 26.pdf

3051-chenp-2005-form 3.pdf

3051-chenp-2005-form 5.pdf

3051-chenp-2005-pct.pdf


Patent Number 234110
Indian Patent Application Number 3051/CHENP/2005
PG Journal Number 22/2009
Publication Date 29-May-2009
Grant Date 05-May-2009
Date of Filing 18-Nov-2005
Name of Patentee F. HOFFMANN-LA ROCHE AG
Applicant Address 124 GRENZACHERSTRASSE, CH-4070 BASEL,
Inventors:
# Inventor's Name Inventor's Address
1 PETERS, JENS-UWE WINKELMATTEN 8, D-79639 GRENZACH-WYHLEN,
2 GALLEY, GUIDO KATZENBUCKELWEG 14, D-79618 RHEINFELDEN,
3 GOODNOW, ROBERT, ALAN, JR 799 LONG HILL ROAD, MORRIS COUNTY, GILLETTE, NEW JERSEY 07933,
PCT International Classification Number A61K 31/553
PCT International Application Number PCT/EP04/05177
PCT International Filing date 2004-05-14
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 03011040.7 2003-05-19 EUROPEAN UNION