Synthesis of 2,4-diaminoquinazolines and tricyclic quinazolines by cascade reductive cyclization of methyl N-cyano-2-nitrobenzimidates

J Org Chem. 2012 Mar 16;77(6):2649-58. doi: 10.1021/jo2023697. Epub 2012 Feb 24.

Abstract

An efficient route to N(4)-substituted 2,4-diaminoquinazolines has been developed by employing tandem condensation of cyanoimidate-amine and reductive cyclization in iron-HCl system. This method is tolerant of a following intramolecular N-alkylation and produces two fused heterocycles in a one-pot procedure. This protocol is a facile two-step synthesis of tricyclic quinazolines, which is effected by potent cyanoimidation and tandem reductive cyclization from 2-nitrobenzaldehydes. Moreover, the forming process of tricyclic quinazolines has been investigated from the ring-opening/ring-closing cascade point of view. It is found that the preparation of tricyclic quinazolinones in good yields relies on the selective hydrolysis of tricyclic quinazolines in base or acid system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents, Tricyclic / chemistry*
  • Antidepressive Agents, Tricyclic / pharmacology
  • Cyclization
  • Imidoesters / chemistry*
  • Molecular Structure
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry*

Substances

  • Antidepressive Agents, Tricyclic
  • Imidoesters
  • Quinazolines
  • 2,4-diaminoquinazoline