Patent GB-1253741-A (GB)
Title: A process for the manufacture of quinoline derivatives
Inventor: GUTZWILLER J A W
IPC: C07D453/04
Filed: 1969-07-02
Abstract: 1,253,741. Quinoline derivatives. F. HOFFMANN-LA ROCHE & CO. A.G. 2 July, 1969 [2 July, 1968], No. 33311/69. Heading C2C. Quinoline derivatives of the Formulµ I and II: wherein E 1  is H, OH, halogen, C 1-7  alkyl, C 1-7  alkoxy or methylenedioxy, R 2  is C 1-7  alkyl or C 2-7  alkenyl and m is 1 or 2, with the proviso that when R 1  is methylenedioxy m is 1, the compounds of Formulµ I and II being novel provided that when (R 1 ) m  is H, OH or C 1-7  alkoxy in position 6, R 2  is other than vinyl or ethyl, and their antipodes and racemates and acid addition salts thereof are prepared by treating compounds of Formulµ V and VI: these compounds being novel provided that when (R 1 ) m  is H, OH or OCH 3  in position- 6, R 2  is other than vinyl or ethyl, their racemates or antipodes thereof with a stereoselective reducing agent, if desired reducing any compound obtained in which R 2  is C 2-7  alkenyl to give corresponding compounds in which R 2  is C 2-7  alkyl, and also, if desired, converting bases obtained into acid addition salts. Compounds of Formulµ V and VI above are obtained by cyclizing compounds of the general Formula IV: X is halogen, with the proviso that when (R 1 ) m  is H or OCH 3  in position 6 and R 2  is vinyl or ethyl, X is other than bromine, or antipodes or racemates thereof, or compound of general Formula X above, where R<SP>1</SP> 2  is C 1-7  alkyl or antipodes or racemates thereof, or compounds of the general Formula X above, wherein R is H or C 1-5  alkyl or antipodes or racemates thereof, by means of a cyclization agent, dehalogenating the product obtained from compounds of Formula Xa or antipodes or racemates thereof and, if desired, converting the so-obtained bases into acid addition salts. The following intermediates are prepared:- α - [1 - Benzoyl - 3 - ethyl - 4 - piperidylmethyl]- # - oxo - # - (7 - methoxy - 4 - quinolyl)propionic acid ethyl ester, α-[1-benzoyl-3-ethyl-4-piperidylmethyl] - # - oxo - # - (6,7 - dimethoxy - 4- quinolyl)propionic acid ethyl ester, α-[1-benzoyl - 3 - ethyl - 4 - piperidylmethyl] - # - oxo - #- (6 - methyl - 4 - quinolyl)propionic acid ethyl ester, α - [1 - benzoyl - 3 - ethyl - 4 - piperidylmethyl] - # - oxo - # - (6 - chloro - 4 - quinolyl)propionic acid ethyl ester, α-[l-benzoyl-3-ethyl-4- piperidylmethyl] - # - oxo - # - (7 - chloro - 4- quinolyl)propionic acid ethyl ester, α-[1-benzoyl - 3 - vinyl - 4 - piperidylmethyl]- # - oxo - #- (7 - chloro - 4 - quinolyl)propionic acid ethyl ester, 7<SP>1</SP> - methoxydihydrocinchotoxine, 6<SP>1</SP>,7<SP>1</SP>- dimethoxy - dihydrocinchotoxine, 6<SP>1</SP> - dimethyldihydrocinchotoxine, 6<SP>1</SP> - chlorodihydrocinchotoxine, 7<SP>1</SP> - chlorodihydrocinchotoxine, 7<SP>1</SP>- chlorocinchotoxine, N - chlorodihydroquinotoxine, N - chloro - 7<SP>1 </SP>- methoxydihydrocinchotoxine, N - chloroquinotoxine, N - chloro - 6<SP>1</SP>,7<SP>1</SP>- dimethoxydihydrocinchotoxine, N - chloro- 6<SP>1</SP> - methyldihydrocinchotoxine, N - chloro - 6<SP>1</SP>- chlorodihydrocinchotoxine, N - chloro - 7<SP>1</SP>- chlorodihydrocinchotoxine, N - chloro - 7<SP>1</SP>- chlorocinchotoxine, 3 - (1 - chloro - 3 - ethyl- 4 - piperidine)propionic acid ethyl ester, 3- [3 - (2 - chloroethyl) - 4 - piperidine]propionic acid ethyl ester trifluoroacetate, 3-[1-benzoyl-3- (2 - chloroethyl) - 4 - piperidine]propionic acid ethyl ester, 3-[1-benzoyl-3-(2-iodoethyl)-4-piperidine]propionic acid ethyl ester, and 3-[1- benzoyl - 3 - vinyl - 4 - piperidine]propionic acid ethyl ester. The above intermediates are obtained in one or more of the possible configurations. Pharmaceutical compositions, having antimalarial and antiarrhythmic properties, contain the above novel compounds of Formulµ I, II, V and VI, or acid addition salts thereof, in association with compatible pharmaceutical carriers. The compositions may be in a forms suitable for oral, parenteral or rectal administration.