Patent GB-1102428-A (GB)
Title: Cycloaliphatic amines and process for their manufacture
IPC: C07D213/30
Filed: 1965-10-18
Abstract: The invention comprises cycloaliphatic compounds with 5-8 ring carbon atoms substituted by (a) an amino group attached to one ring carbon atom and (b), attached to different ring carbon atoms, one or two heterocyclic radicals of aromatic character, or one aryl radical or one heterocyclic radical of aromatic character, together with two radicals selected from aryl radicals, heterocyclic radicals of aromatic character and cycloaliphatic radicals, with the proviso that, if three substituents of aromatic character are present, at least two are separated from the amino substituent by at least three ring carbon atoms, and N-oxides and salts of these compounds, and especially compounds of the general formula <FORM:1102428/C2/1> (wherein R1 represents H or lower (i.e. up to C7 alkyl, R2 represents H, lower alkyl, di-(lower alkyl)-amino-lower alkyl or lower alkyleneimino-lower alkyl, or R1 and R2 jointly represent lower alkylene or aza-, oxa- or thia-lower alkylene, R3 and R7 each represent H or lower alkyl, R4 and R6 each represent a cycloalkyl radical or one of the radicals mentioned for R5, and R5 represents an aryl radical or a heterocyclic radical of aromatic character, these aryl and heterocyclic radicals each being unsubstituted or carrying one or more lower alkyl or alkoxy, halo, CF3 or di-(lower alkyl)-amino substituents, and the heterocyclic radical containing one or two N atoms or an O or S atom as ring member(s)), and their 3-hydroxy or 3-acyloxy derivatives (acyl being the radical of a lower fatty acid or a monocyclic aryl sulphonic acid), or their didehydro derivatives in which the double bond extends from the 3-position, and salts thereof, and the preparation of these compounds by (1) the action of ammonia, a primary or secondary amine, or hydroxylamine, and a reducing agent, on a starting material differing from the desired product by having a ketonic oxygen atom in the position to be occupied by substituent (a), or (2) the action of an appropriate aromatic metal compound on a starting material differing from the desired product by having a ketonic oxygen atom in a position to be occupied by an aromatic substituent (b), or (3) the action of ammonia or a primary or secondary amine on a starting material differing from the desired product by having a reactively esterified OH group (especially a halogen atom) in the position to be occupied by substituent (a).  Thereafter in all cases, if desired, substituents may be introduced, split off or interconverted, salts may be converted into free bases or into other salts, free bases may be converted into salts, quaternary ammonium derivatives or N-oxides, and/or mixtures of isomers may be separated into single isomers.  The preparation of the following starting materials is described: 3,5-diphenyl-4-(2-pyridyl) - cyclohexanone (via 3,5 - diphenyl - 3 - hydroxy - 4- (2 - pyridyl) - cyclohexanone and 3,5 - diphenyl - 4 - (2 - pyridyl) - cyclohex - 2 - enone, with formation of 1,3-diphenyl-2-(2-pyridyl) - hexane - 1,5 - dione as a by-product in the first stage); 3,4,5-triphenylcyclohexanol and its p-toluenesulphonic ester; 3b ,4a , 5b -triphenylcyclohexanone; 3,5 - diphenyl - 4 - (4-pyridyl) - cyclohexanone (via 3,5 - diphenyl-4-(4 - pyridyl) - cyclohex - 2 - enone and 3,5-diphenyl - 1 - hydroxy - 4 - (4 - pyridyl) - cyclohexane); 3,5 - di - (2 - furyl) - 4 - (2 - pyridyl)-cyclohexanone (via 3,5 - di - (2 - furyl) - 4 - (2-pyridyl) - cyclohex - 2 - enone); 3,5 - diphenyl-4-(4 - pyrimidyl) - cyclohexanone (via 3,5 - diphenyl - 3 - hydroxy - 4 (4 - pyrimidyl)-cyclohexanone and 3,5-diphenyl-4-(4-pyrimidyl)-cyclohex - 2 - enone); 3,5 - diphenyl - 4 - (2-quinolinyl) - cyclohexanone (via 2 - phenacyl-quinoline, 3,5 - diphenyl - 3 - hydroxy - 4 - (2-quinolinyl) - cyclohexanone and 3,5 - diphenyl-4 - (2 - quinolinyl) - cyclohex - 2 - enone); 3b ,5b  - di - (4 - methoxyphenyl) - 4a  - (2 - pyridyl) - cyclohexanone (via 4-methoxybenzalacetone, 4 - methoxy - a  - (2 - pyridyl) - acetophenone, 3 - hydroxy - 3,5b  - di - (4 - methoxyphenyl) - 4a  - (2 - pyridyl) - cyclohexanone and the corresponding D 2-compound); 3b ,5b -di-(4-chlorophenyl) - 4a  - (2 - pyridyl) - cyclohexanone (via 4 - chlorobenzalacetone, 4 - chloro-a  - (2 - pyridyl) - acetophenone, 3,5b  - di - (4-chlorophenyl) - 3 - hydroxy - 4a  - (2 - pyridyl)-cyclohexanone and 3,5b -di-(4-chlorophenyl)-4a  - (2 - pyridyl) - cyclohex - 2 - enone); 3b  - (4-chlorophenyl) -4a  - (2 - pyridyl) - 5b  - (4-methoxyphenyl) - cyclohexanone (via 5b -(4-chlorophenyl) - 3 - hydroxy - 3 - (4 - methoxyphenyl)-4a  - (2 - pyridyl) - cyclohexanone and 3b -(4-chlorophenyl) - 5b  - (4 - methoxyphenyl) - 4a -(2-pyridyl) - cyclohexanone); 3b ,5b  - di - (3,4,5-trimethoxyphenyl) - 4a  - (2 - pyridyl) - cyclohexanone (via 3,4,5 - trimethoxybenzalacetone, a  - (2 - pyridyl) - 3,4,5 - trimethoxyacetophenone, 3 - hydroxy - 4a  - (2 - pyridyl) - 3,5b -di - (3,4,5 - trimethoxyphenyl) - cyclohexanone and 4a  - (2 - pyridyl) - 3,5b  - di - (3,4,5 - trimethoxyphenyl) - cyclohex - 2 - enone); 4-pyrrolidinocyclohexanone (via 4-benzoyloxy-1-pyrrolidinocyclohexane and 4-pyrrolidinocyclohexanol); 4 - (2 - pyridyl) - cyclohexanone (via 4 - hydroxy - 4 - (2 - pyridyl) - cyclohexanone and 4 - (2 - pyridyl) - cyclohex - 3 - enone); 1b -(4 - bromobenzenesulphonyloxy) - 3b ,5b  - diphenyl - 4a  - (2 - pyridyl) - cyclohexane ( via 3b ,5b - diphenyl - 1b  - hydroxy - 4a  - (2-pyridyl)-cyclohexane); 3b ,5b - diphenyl - 4a  - (2-pyridyl)-cyclopentanone (via 2,6 - dibromo - 3b ,5b  - diphenyl - 4a  - (2 - pyridyl) - cyclohexanone and 3b ,5b  - diphenyl - 1 - hydroxy - 4a  - (2 - pyridyl)-cyclopentanecarboxylic acid); 4 - cyano - 3,5-diphenyl - 4 - (2 - pyridyl) - cyclohexanone); 3b ,5b  - diphenyl - 4a  - (2 -pyridyl) - cyclooctanone (via 8-ethoxycarbonyl-3b ,5b -diphenyl-4a -(2 - pyridyl) - 1 - pyrrolidino - 6,8 - cyclooctadiene, 8 - ethoxycarbonyl - 3b ,5b  - diphenyl-4a -(2 - pyridyl) - cyclooct - 7 - enone and 8-ethoxycarbonyl - 3b ,5b - diphenyl - 4a  - (2 - pyridyl)-cyclooctanone); and 3,4-diphenyl - 5 - (4-pyridyl)-cyclohex-2-enone.  Pharmaceutical and veterinary preparations (e.g. tablets, dragees, suppositories, capsules, solutions, suspensions, emulsion or animal feedstuffs or feed additives), for enteral or parenteral administration as hypotensives and diuretics, comprise the compounds of the invention in admixture or conjunction with a pharmaceutically suitable carrier.