A practical synthesis of 1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid derivatives from pyrrole-2-carboxaldehydes

• Published in: Tetrahedron Vol. 49; no. 36; pp. 8139 - 8146
• Main Authors: Dekhane, Mouloud, Potier, Pierre, Dodd, Robert H.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 03.09.1993; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; BRAIN BENZODIAZEPINE RECEPTORS; PROCONVULSANT; PYRROLE; HYBRID MOLECULES; ANALOGS; BETA-CARBOLINE DERIVATIVES; MICE; Lewis acid; Bicyclic compound; Condensation reaction; Enaminoester; Cyclization; Nitrogen heterocycle
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(01)88033-9

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 β-carboline-3-carboxylates ( 1), was developed. Thus, condensation of 1-(p-toluenesulfonyl)pyrrole-2-carboxaldehyde ( 4) and ethyl α-amino-β,β-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. The title compounds were obtained in high yields after reduction and titanium (IV) chloride catalyzed cyclization of imine 8, itself obtained by condensation of pyrrole-2-carboxaldehyde 4 and the α-formylglycine equivalent 6.