A one-step ring transformation/ring annulation approach to pyrrolo[2,3-d]pyrimidines. A new synthesis of the potent DHFR inhibitor TNP-351

Article abstract of DOI:10.1021/jo00126a017

Condensation of amidines with 2-amino-3-cyanofurans gives 2-substituted-4-aminopyrrolo[2,3-d]pyrimidines by a ring-opening, ring-recyclization sequence of reactions through which the starting furan 2-amino nitrogen becomes the pyrrole nitrogen of the final product and one of the amidine nitrogens becomes N-1 of the fused pyrimidine ring. 2,4-Diamino-5-[2-(4-carbethoxyphenyl)ethyl]pyrrolo[2,3-d]pyrimidine, a key intermediate in the synthesis of the DHFR inhibitor TNP-351, has been prepared in one step by reaction of ethyl 4-[2-(2-amino-3-cyanofuran-4-yl)ethyl]benzoate with guanidine.