method for the preparation of medicines for the treatment of acute reduced contractile ability of the heart.and method for preparation of medicinal compounds suitable for this application.

摘要

1392674 Dopamine derivatives ELI LILLY & CO 9 April 1973 [12 April 1972] 16835/73 Heading C2C The invention comprises dopamine derivatives of Formula (I) in which R and R 1 are H or CH 3 , at least one being H; R 2 and R 3 are H or OH at least one being OH; n is 1 or 2; and when n is 1 and R 2 and R 3 are both OH, then either R or R 1 is CH 3 ; and the pharmaceutically acceptable addition salts thereof with mineral acids. They may be prepared by reacting a compound of Formula (II) in which R 1 is hydrogen, R 2 SP1/SP and R 3 SP1/SP are H or CH 3 O- at least one being methoxy, n is 1 or 2; and when n is 1 and R2SP1/SP and R 3 SP1/SP are both CH 3 O, then R or R 1 is CH 3 ; with hydrobromic acid and optionally converting to pharmaceutically acceptable salts. The methyl ethers used as starting materials may be prepared as follows: (a) the compounds of Formula II in which R is methyl and R 1 is hydrogen are prepared by the reductive alkylation of a methoxylated phenylethylamine or a methoxylated phenyl propyl amine with 3,4-dimethoxyphenylacetone; (b) the compounds in which R is methyl and R 1 is hydrogen may also be prepared by reacting 3,4- dimethoxyphenylacetone with a methoxylated phenethylamine or a methoxylated phenylpropylamine in the presence of p-toluene sulphonic acid to form the imine which is then reduced to the secondary amine; (c) the compounds in which R is hydrogen and R 1 is methyl may be prepared by the reductive alkylation of 3,4-dimethoxyphenylethylamine with the desired mono- or dimethoxylated phenyl butane-3-one (n=2) or the mono- or di-methoxylated phenylacetone (n = 1); (d) the compounds in which R is hydrogen and R 1 is methyl may also be prepared by the condensation of 3,4-dimethoxyphenylacetic acid with a methoxylated 1 -phenyl-3-aminobutane (n=2) or with a methoxylated 1-phenyl-2- aminopropane (n =1) to form as an intermediate the methoxylated amide which is reduced under nitrogen with borane to provide the secondary amine; and (e) the compounds in which R and R 1 are both hydrogen may be prepared by the alkylation of 3,4-dimethoxyphenylethylamine with a methoxylated phenyl-n-propyl bromide (n=2) or with a methoxylated phenyethyl bromide (n= 1). The products of Formula (I) are used in pharmaceutical agents.