Synthesis of a novel tetracyclic azaindolo[2,1-c][1,4]benzoxazine ring system

Synthesis of a series of novel fused tetracyclic mono- and diazaindolo[2,1-c][1,4]benzoxazine heterocyclic compounds 3a-o has been achieved in a two-step one-pot reaction set up starting from commercially available or easily accessible inputs. For example, reaction of di-lithiated (N-Boc)-2-amino-3-methylpyridine Li(2)-2a with Weinreb amide of 2-(2,4-difluorophenoxy)-2,2-dimethylacetic acid la, followed by TFA treatment furnished the tetracyclic compound 3a, which is essentially a fusion of 7-azaindole and 3,4dihydro[1,4]benzoxazine, in 70% isolated yield. A competitive elimination by-product 4a was also observed (24% isolated yield) in this case. Based on our initial results, a structural basis and molecular mechanism have been suggested to explain these two parallel reactions. Consequently, with appropriate structural tuning of 1, formation of the individual products can be controlled. (C) 2011 Elsevier Ltd. All rights reserved.