Patent GB-1489486-A (GB)
Title: Esters of thienobenzopyrans and thiopyrano benzopyrans
IPC: C07D333/38
Filed: 1975-03-05
Abstract: 1489486 Esters of thienobenzopyrans and thiopyranobenzopyrans L S HARRIS H G PARS J C SHEEHAN and R K RAZDAN 5 March 1975 [5 March 1974] 9212/75 Addition to 1386027 Heading C2C Novel compounds of the Formula I wherein n is 0 to 3, m is 0-3 provided m + n is 2 or 3, R 1  is alkyl, R 2  is C 1-20  alkyl, C 3-8  cycloalkylalkyl or alkylcycloalkylalkyl, R 4  is hydrogen or alkyl, R 5  is hydrogen or alkyl and R 3  is in which Y is C 1-8  alkylene, a is 1 to 4, b is 1 to 4, R 6  is hydrogen or alkyl and X is CH 2 , O, S or NR 7  wherein R 7  is hydrogen or alkyl with the proviso that (a) when X is O, S or NR 7 , a and b are both 2 and (b) Y is a branched chain alkylene group and/or at least one of R 4 , R 5  and R 6  is alkyl wherein cycloalkyl and alkylcycloalkyl moieties have 3 to 8 carbon atoms and alkyl groups unless otherwise specified are C 1-6 , and acid addition salts thereof may be prepared by esterification of a compound of the formula X with an acid R 3 OH or a salt thereof in the presence of a slight excess of a carbodiimide. The intermediates of the Formula X are prepared by cyclizing an appropriately substituted oxo-tetrahydrothiopyran carboxylate or oxo-tetra hydrothiophene carboxylate in which the oxo and carboxylate groups are on adjacent carbon atoms of the ring with an R 2  substituted resorcinol to form a thienobenzopyran or thiopyranobenzopyran of the Formula X in which the R 1  radicals together form an oxo group and subsequently reacting this product with an appropriate Grignard reagent. Ethyl 5 - methyl - 3 - oxo - tetrahydrothiophene-2-carboxylate is prepared by reaction of ethyl mercaptoacetate with ethyl crotonate in the presence of sodium ethoxide to yield diethyl - 4 - methyl - 3 - thiahexanediote followed by cyclization using strong base. Ethyl 5,5- dimethyl - 3 - oxo - tetrahydrothiophene - 2 - carboxylate is prepared by a similar method. Methyl 4 - methyl - 3 - oxotetrahydrothiopyran-2-carboxylate is prepared by reacting 2- methyl-4-butyrolactone with methanolic hydrogen bromide to yield methyl 4-bromo-2-methylbutyrate, followed by condensation of the product with methylmercaptoacetate in base to form methyl 4 - (methoxycarbonylmethylthio)- 2- methyl butyrate followed by cyclization using strong base to yield the required compound. 2 - Methyl - 4 - piperidinobutyric acid hydrochloride is prepared by condensation of 4- bromo-2-methyl butyrate with piperidine to yield ethyl - 2 - methyl - 4 - piperidino butyrate followed by treatment with hydrochloric acid. 2,2 - Dimethyl - 4 - piperidino butyric acid hydrochloride is prepared by reaction of 2,2- dimethyl - 4 - butyrolactone with ethanolic hydrogen bromide to yield ethyl 2,2-dimethyl-4- bromobutyrate which with piperidine yields ethyl 2,2 - dimethyl - 4 - piperidinobutyrate which yields the required compound on treatment with hydrochloric acid. Pharmaceutical compositions of the compounds I with the usual excipients show analgesic, antianxiety, tranquillizing, sedative, antidepressant, anti-convulsant and anti-psychotic activity when administered orally or parenterally.