ACETAMIDINE DERIVATIVES PROCESS FOR PREPARING THE SAME AND PHARMA CEUTICAL USES THEREOF

摘要

1380145 Acetamidine derivatives, process for preparing the same and pharmaceutical uses thereof LABAZ 26 April 1973 [2 May 1972] 20436/72 Heading C2C The invention comprises compounds of formula and the pharmaceutically acceptable single (mono), and double (di), acid addition salts thereof, wherein A-B represents CH-CH or C=C, R represents hydrogen or a C 1-4 alkyl group, Y represents 0, a CH 2 or -CH-CH 3 group, or an NH or substituted NH group, n is an integer of from 1 to 3, and m is 2 or 3. These compounds may be obtained by reacting in an inert organic medium an iminoester salt of formula wherein A-B and R have the same meanings as defined above, R 1 represents a C 1-4 alkyl radical and X represents the anion of a strong inorganic acid, with a secondary cyclic amine of formula wherein Y, n and m have the meanings given above to form the corresponding salt of the required acetamidine derivative which if required, can either be converted to a double salt by reaction with the required quantity of the appropriate acid or be reacted with a base to give the corresponding acetamidine derivative in free base form which, if desired, may then be reacted with a stoichiometric quantity of an organic or inorganic acid to form a different single or double pharmaceutically acceptable acid addition salt. In Example I, the following intermediates are prepared: 2-ethyl-3-chloromethylbenzofuran by the reaction of 2-ethylbenzofuran with HCl (see also Example 4(a)); 2 - ethyl - 3 - cyanomethyl - benzofuran by the reaction of 2-ethyl-3-chloromethyl-benzofuran with KCN (see also Examples 4(b), 6(c) and 7(b)); ethyl (2 - ethyl - 3 - benzofuranyl) - iminoacetate hydrochloride by the reaction of 2-ethyl 3-cyanomethyl-benzofuran with ethanol and HCl (see also Examples 3(a), 4(c), 5(a), 6(d) and 7(c)). The intermediate (2-ethyl-2,3-dihydro-3- benzofuranyl) - acetic acid of Example 6 is obtained by reducing (2-ethyl-3-benzofuranyl)- acetic acid, and 2-(2-ethyl-2,3-dihydro-3-benzofuranyl)-acetamide by treating (2-ethyl-2,3- dihydro-3-benzofuranyl)-acetyl chloride with NH 3 (see also Example 7(a)). The invention also comprises a pharmaceutical composition which contains as an active ingredient a compound according to the invention in association with a pharmaceutical carrier.