A PRACTICAL SYNTHESIS OF 1H-PYRROLO[2,3-C]PYRIDINE-5-CARBOXYLIC ACID-DERIVATIVES FROM PYRROLE-2-CARBOXALDEHYDES

As part of a study concerning benzodiazepine receptor-ligand interactions, an efficient synthesis of 1H-pyrrolo[2,3-c]pyridine-5-carboxylates (i.e., 6-azaindole-5-carboxylates, 2), structurally related to the highly active beta-carboline-3-carboxylates (1), was developed. Thus, condensation of 1-(p-toluenesulfonyl)pyrrole-2-carboxaldehyde (4) and ethyl alpha-amino-beta,beta-diethoxypropionate (6) followed by reduction of the resulting imine bond gave the amino intermediate 13 which cyclized cleanly in the presence of titanium (IV) chloride to furnish, after detosylation, 2b in preparatively useful yields. This route is potentially applicable to the preparation of multiply-substituted 6-azaindole derivatives.