4-(2-hydroxy-3-amino-propoxy)-indole-2-carboxy- - lic acids and esters and 2-hydroxymethylindoles as beta

摘要

4-(2-Hydroxy-3-amino-propoxy)-indole-2-carboxylic acids and esters and 2-hydroxymethylindoles as betadrenergic agents and intermediates M3A. Are new compounds of formulae (Ia) and Ib) and their salts. (where R1=opt. branched 1-5C alkyl, cyclo alkyl, 8-10C-phenylalkyl or 1-adamantyl; R2=H or 1-5C alkyl). They are prepared by (a) reacting an appropriate 3-halo-2-hydroxypropoxy indole or an epoxypropoxy indole with R1NH2, (b) hydrogenolysis of the N-benzyl derivs. of (Ia) or (Ib), (c) reduction of the Schiffs base derived from (Ia or Ib where R1=H) with a ketone R3COR4 (where R3 and R4=lower alkyl) with simultaneous reduction of COOR to -CH2OH (d) reduction of (Ia) to (Ib) and (e) hydrolysis of (Ia, R2=alkyl) to the free acid or esterification of (Ia E2-H). Compounds (II), useful as intermediates where R'2 = 1-5 alkyl are prepared by reacting 2-benzyloxy-6-nitro-toluene with an oxalic acid ester and reductively cyclising the product. Prefd. compounds are (Ia) and (Ib) R1=iso-P2 and R2=H, Me or Et, R1=tert-Bu and R2=H or Et, R1=tert pentyl and R2=Et, R1=cyclopropyl, and R2=Et; (Ib) R1=sec-Bu, 3-pentyl, adamantyl and Me; and (II) R'2=Me and Et.