A new methodology for the synthesis of 3-amino-1H-indole-2-carboxylates

Jitendra Rameshlal Harjani, Andrew X Tang, Raymond Stanley Norton, Jonathan Bayldon Baell

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

A new methodology has been developed for the synthesis of 3-amino-1H-indole-2-carboxylates. 2-Aminobenzonitriles were protected as benzyl (2-cyanophenyl)carbamates and converted into corresponding glycinate esters using sodium hydride and bromoacetate esters. Sodium hydride efficiently promotes the addition of the glycinate a-carbon to the cyano group at low temperatures, resulting in the formation of the desired indole core with 3-amino and 2-carboxylate groups. This new methodology uses Pd-C mediated hydrogenolysis with molecular hydrogen, providing neutral conditions for removal of the N-carbamate protecting group. This methodology demonstrates good functional group tolerance towards a variety of substituents in the aromatic ring and ester groups. The overall yield of 3-amino-1H-indole-2-carboxylates obtained by this four-step methodology is at least 30 or higher with yields as high as 50 realised for three of the indoles investigated in this study.
Original languageEnglish
Pages (from-to)8047 - 8055
Number of pages9
JournalTetrahedron
Volume70
Issue number43
DOIs
Publication statusPublished - 2014

Cite this