GB1187706A - 2-Aminomethyl-2,3-Dihydro-Benzofurans - Google Patents

Abstract

1,187,706. Coumaran derivatives. CIBA Ltd. 7 June, 1968, No. 27312/68. Heading C2C. Novel coumaran derivatives of the formula wherein R 1 is an aryl radical or a heterocyclic radical of aromatic character, each of alk 1 and alk 2 is C 2-7 alkylene separating the nitrogen atom by 2 carbon atoms, each of R 2 and R 3 is H or C 1-7 alkyl, and Ph is a 1,2-phenylene radical, and acid addition and quaternary ammonium salts thereof, are prepared by condensing compounds of the formula R 1 -Y and X-CH(R 2 )-Z, in which Z is the appropriate 2,3-dihydrobenzofuran radical, and one of X and Y represents a halogen atom or a bis- (#- halogeno - C 1-7 alkyl) - amino group and the other an appropriately substituted piperazino radical or NH 2 , both X and Y together containing 2 N atoms only, or reacting compounds of the formula R 1 -NH-alk 1 NHCH(R 2 )-Z and Z 1 -alk 2 -Z 2 , in which Z 1 and Z 2 are halogen, or compounds wherein R 2 is H, by reducing the corresponding 1-R 1 -4- (2,3 - dihydrobenzofuroyl) - piperazine derivative, and if desired, converting a resulting compound into an acid addition or quaternary ammonium salt, and/or resolving a mixture of isomers into the single isomers by formation of salts with optically active acids. 2 - Bromomethyl - 5 - acetyl - 2,3 - dihydrobenzofuran is obtained by the ring closure of 3- (2,3 - dibromopropyl) - 4 - acetoxyacetophenone resulting from the bromination of 3-allyl-4- acetoxyacetophenone, which is in turn obtained by heating a mixture of acetic anhydride and 4- allyloxy-acetophenone, obtained by treating 4- hydroxyacetophenone with allyl bromide. By a similar process 2 - bromomethyl - 7 - acetyl - 2,3- dihydrobenzofuran is obtained from 2-hydroxyacetophenone. 2 - Aminomethyl - 5 - acetyl - 2,3 - dihydrobenzofuran is obtained by the hydrolysis of the phthalimide resulting from treating 2-bromomethyl - 5 - acetyl - 2,3 - dihydrobenzofuran with potassium phthalimide. N - phenyl - N<SP>1</SP> (7 - acetyl - 2,3 - dihydro - 2- benzofuryl) - methyl - ethylenediamine is made by reacting N-phenylethylenediamine with 2-bromomethyl - 7 - acetyl - 2,3 - dihydrobenzofuran. Pharmaceutical compositions, suitable for enteral or parenteral administration and having adrenergic blocking and hypotensive activities, contain the above novel 2,3-dihydrobenzofuran derivatives or acid addition and quaternary ammonium salts thereof as the active ingredient and pharmaceutically acceptable carriers.