Patent GB-1210106-A (GB)
Title: Derivatives of 1,2,3,4-tetrahydrobenzothieno [2,3-c]pyridine and of 1,2,3,4-tetrahydro-5h-benzothieno[2,3-c]azepine
IPC: C07D495/04
Filed: 1968-03-06
Abstract: 1,210,106. 1,2,3,4-Tetrahydrobenzothieno[2,3- c]pyridine and 1,2,3,4 - tetrahydro - 5H - benzothiene[2,3-c]azepine derivatives. COLGATEPALMOLIVE CO. 6 March, 1968 [8 March, 1967 (2); 6 Feb., 1968 (2)], No. 10892/68. Heading C2C. Novel 1,2,3,4 - tetrahydrobenzothieno[2,3 - c] pyridine and 1,2,3,4 - tetrahydro - 5H - benzothieno[2,3-c]azepine derivatives of the general formula wherein A and A 1  are the same or different and are hydrogen or halogen atoms or hydroxy, nitro, C 1-4  alkyl, C 1-3  alkoxy or trifluoromethyl groups; m is 1 or 2; R is a hydrogen atom or a C 1-4  alkyl, C 7-11  aralkyl, -(CH 2 ) n OH (in which n is from 2 to 6), B-Am, -COOR 1 , -COBAm or amidino group, in which B is a single chemical bond or a C 1-6  alkylene group; R 1  is a C 1-4   alkyl, di-(C 1-4  alkyl)amino-C 1-4  alkyl, hydroxy- C 1-4  alkyl, C 3-6  alkenyl, C 7-11  aralkyl, C 3-7  cycloalkyl or C 3-7  cycloalkyl-C 1-4  alkyl group; and Am is (a) -NR 2 R 3  in which R 2  and R 3  are the same or different and are hydrogen atoms or C 1-4  alkyl, di-(C 1-4  alkyl)-amino-C 1-4  alkyl, hydroxy-C 1-4  alkyl, C 3-6  alkenyl, C 3-7  cycloalkyl or C 3-7  cycloalkyl-C 1-4  alkyl groups; (b) a morpholino, pyrrolidino, piperidino, N-C 1-4  alkyl - piperazino, N - (phenyl - C 1-4  alkyl). piperazino or N-(hydroxy C 1-4  alkyl)-piperazino group; or (c) a piperidyl or pyrrolidyl radical bonded through a nuclear carbon atom to B; and X 1  and X 2  are the same or different and are hydrogen atoms or C 1-4  alkyl, phenyl, halo- or alkoxy-substituted phenyl, C 7-11  aralkyl, piperidyl, pyridyl, furyl, pyrryl, pyrrolidyl or B-Am groups, provided that X 2  is not a hydrogen atom when X 1  and R are both hydrogen atoms; and pharmaceutically acceptable acid addition and quaternary ammonium salts thereof are prepared, for example, (a) when R is a hydrogen atom and X 1  is a C 1-4  alkyl group, by treatment of a 3-thianaphthenyl-alkylamine of the general formula with an aldehyde or ketone of the general formula X 1 COX 2  in the presence of p-toluenesulphonic acid and toluene, followed by treatment with an acid; (b) when R and X 1  are hydrogen atoms, by reduction of a 3,4-dihydrothianaphtheno[2,3-c]pyridine or 3,4-dihydro- 5H - benzothieno[2,3 - c] - azepine derivative of the general formula and (c) when R is a C 1-4  alkyl or C 7-11  aralkyl group, by treatment of a compound of the first general formula above wherein R is a hydrogen atom with a compound of the general formula RX in which R is a C 1-4  alkyl or C 7-11  aralkyl group and X is a halogen atom, followed optionally by conversion of the product to a pharmaceutically acceptable acid addition or quaternary ammonium salt thereof. Pharmaceutical compositions having antipsychotic, anti - hypertensive and central nervous system stimulant activity comprise, as active ingredient, a 1,2,3,4-tetrahydrobenzothieno[2,3-c]pyridine or 1,2,3,4-tetrahydro-5H- benzothieno[2,3-c]azepine derivative of the first general formula above or a pharmaceutically acceptable acid addition or quaternary ammonium salt thereof, and a pharmaceutically acceptable carrier. 1 - Methyl - 3,4 - dihydrothianaphtheno[2,3-c]- pyridine is prepared by reduction of 3-cyanomethylthianaphthene with lithium aluminium hydride, treatment of the resulting #-(3-thianaphthenyl) - ethylamine with acetic anhydride and treatment of the N-[13-(3-thianaphtenyl)- ethyl]acetamide so obtained with phosphorus oxychloride and phosphorus pentoxide.