Synthesis of Folate Antimetabolites A Furan to Pyrrole Transformation

Synthesis of Folate Antimetabolites A Furan to Pyrrole Transformation 

Reaction of o-aminonitriles with guanidine is a widely used and efficient method for the preparation of condensed 2,4-diaminopyrimidines, 1 2. This procedure was adopted with a 

The reactions with the aminocyanofiirans produced an unexpected result, however, as illustrated by the following example. 2-Amino-3-cyano-4-methylfuran was added to a solution of guanidine free base in ethanol, and the mixture was heated under reflux for 24 hours. Standard work-up gave the pyrrolo[2,3-d]pyrimidine 3 in 67% yield, and not the expected furo[2,3- /]pyrimidine. 

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