A Synthetic Route to Tetrahydro-1 H-azepino[4,3,2- cd]indoles via Ring-Opening Cyclization of Activated Azetidines with 4-Bromoindole: Toward a Vasopressin V2 Receptor Antagonist

Gaurav Goswami; Bharat Singh; Imtiyaz Ahmad Wani; Abhijit Mal; Manas K Ghorai

doi:10.1021/acs.joc.4c01270

A Synthetic Route to Tetrahydro-1 H-azepino[4,3,2- cd]indoles via Ring-Opening Cyclization of Activated Azetidines with 4-Bromoindole: Toward a Vasopressin V2 Receptor Antagonist

J Org Chem. 2024 Aug 16;89(16):11576-11587. doi: 10.1021/acs.joc.4c01270. Epub 2024 Aug 5.

Authors

Gaurav Goswami¹, Bharat Singh¹, Imtiyaz Ahmad Wani¹, Abhijit Mal¹, Manas K Ghorai¹

Affiliation

¹ Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India.

PMID: 39102588
DOI: 10.1021/acs.joc.4c01270

Abstract

A simple one-pot, two-step strategy for the synthesis of tetrahydro-1H-azepino[4,3,2-cd]indoles via Lewis acid-catalyzed S_N2-type ring opening of activated azetidines with 4-bromoindole, followed by a Pd-catalyzed intramolecular C-N cyclization reaction, with good to excellent yields is described. Utilizing this protocol, the vasopressin V2 receptor antagonist precursor has been synthesized easily. Enantioenriched tetrahydro-1H-azepino[4,3,2-cd]indoles were obtained by starting from enantiopure azetidine.