Patent EP-0818448-A1 (EP)
Inventor: SCHMIDT GUNTER DR
IPC: C07D221/04
Filed: 1997-06-24
Abstract: Cycloalkano-pyridine compounds of formula (I) and their salts and N-oxides are new. A = 6-10C aryl (optionally up to penta-substituted by halo, NO2, OH, CF3, OCF3, 1-7C alkyl, 1-7C acyl, 1-7C hydroxyalkyl, 1-7C alkoxy or NR3R4); R3, R4 = H, phenyl or 1-6C alkyl; D = 6-10C aryl (optionally substituted by phenyl, halo, NO2, CF3 or OCF3), LR5, C(R6)(R7)R8 or XVTR9; R9 = 3-6C cycloalkyl, 6-10C aryl or 5-7 membered, optionally benzo-condensed, optionally unsaturated mono- bi or tri-cyclic heterocycle with 1-4 S, N and/or O (all optionally up to penta-substituted by halo, NO2, OH, CF3, CN, COOH, OCF3, 1-6C alkyl, 1-6C acyl, 1-6C alkylthio, 1-6C alkoxy or alkoxycarbonyl, 6-10C aryl (optionally substituted by aryl or CF3) or 5-7 membered, optionally benzo-condensed, heteroaryl with 1-3 N, O and/or S heteroatoms), and/or OR10, SR11, SO2R12 or NR13, R14; R10-R12 = 6-10C aryl (optionally mono- to di-substituted, by phenyl, halo or 1-6C alkyl); R5, R6 = as for R9 or a group of formula (a) or (b); R7 = H or halo; R8 = H, halo, N3, CF3, OH, OCF3, 1-6C alkoxy, 1-6C alkyl or NR15R16; or R7+R8 = O or NR17; R17 = H, 1-6C alkyl, 1-6C acyl or 1-6C alkoxy; L = 1-8C alkylene or 2-8C alkenylene (both optionally mono- or di- substituted by OH); T, X = bond or 1-8C alkylene, provided they are not both a bond; V = O, S or NR18; R13-R16, R18 = as R3, R4; E = 3-8C cycloalkyl, 1-8C alkyl (optionally substituted by 3-8C cycloalkyl or OH) or phenyl (optionally substituted by halo or CF3); R1+R2 = 1-7C alkylene substituted by carbonyl and/or Z, and optionally also geminal, optionally substituted by up to 6 Z' and/or up to 5 Z", and/or 1,2-(CH2)c, SO2C6H5, (CO)dNR23R24 or O; and/or a spiro-bonded group Zb of formula (g)-(k); Z = OR19, or a group of formula (c)-(f); a, b = 1-3; R19 = H, 3-7C cycloalkyl, up to 8C silylalkyl, 1-8C alkyl (optionally substituted by OH, 1-6C alkoxy or Ar), (where alkyl is optionally substituted by OR22) ÄsicÜ, 1-20C acyl or benzoyl (optionally substituted by halo, CF3, NO2 or OCF3) or 1-8C fluoroacyl (with 1-9F); R20, R21 = H, phenyl or 1-6C alkyl; or R20+R21 = 3-6C cycloalkyl; Z" = phenyl, benzoyl, thiophenyl or sulphonylbenzyl (all optionally substituted by halo, CF3, OCF3 or NO2); Z' = halo, NO2, N3, OH, CF3, CN, NC, COOH, 3-7C cycloalkyl, 3-7C cycloalkyloxy, 1-6C alkyl (optionally mono- or di-substituted by OH, benzyloxy, CF3, benzoyl, alkoxy, oxyacyl or carboxy each with 1-4C, and/or phenyl (itself optionally substituted by halo, CF3 or OCF3)), 1-6C alkylthio, 1-6C alkoxy or alkoxycarbonyl; R22 = 1-4C acyl or benzyl; Ar = phenyl (optionally substituted by halo, NO2, CF3, OCF3 or phenyl- or tetrazolyl-substituted phenyl); c = 1-4; d = 0 or 1; R23, R24 = H, 3-6C cycloalkyl, 1-6C alkyl, benzyl or phenyl (optionally mono- or di-substituted by halo, CF3, CN, phenyl or NO2); W= O or S; Y+Y' = 2-6C alkylene; e = 1-7; f = 1 or 2; R25-R31 = H, CF3, phenyl, halo, 1-6C alkyl or 1-6C alkoxy; or R25+R26 or R27+R28 = 1-6C alkylene or W-(CH2)h-W; h = 2-8; R32+R33 = 3-7-membered heterocycle containing O, S, SO, SO2 or NR34; R34 = H, phenyl, benzyl or 1-4C alkyl. Also claimed are the following intermediates: 3-amino-3-cyclopentyl-1-(4-trifluoromethylphenyl)propenone; 2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-3-(trifluoromethylbenzoy l)-4,6,7,8-tetrahydro-1H-quinolin-5-one; 2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-3-(4-trifluoromethylbenz oyl)-7,8-dihydro-6H-quinolin-5-one; Ä2-cyclopentyl-4-(4-fluorophenyl)-5-hydroxy-7,7-dimethyl-5,6,7,8-tetra hydroquinolin-3-ylÜ- (4-trifluoromethylphenyl)-methanone; Ä5-(tert. butyldimethylsilanyloxy)-2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl -5,6,7,8-tetrahydroquinolin-3-ylÜ-(4-trifluoromethylphenyl)-me thanone; Ä5-(tert. butyldimethylsilanyloxy)-2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl -5,6,7,8-tetrahydroquinolin-3-ylÜ-(4-trifluoromethylphenyl)-me thanol; and 5-(tert. butyldimethylsilanyloxy)-2-cyclopentyl-4-(4-fluorophenyl)-3-Äfluoro-(4 -trifluoromethylphenyl)-methylÜ-7,7-dimethyl-5,6,7,8-tetrahydr oquinoline.