Structural elucidation of an oxazolo[5,4‐ b ]pyridine: An alternative cyclization product related to nevirapine

An unexpected cyclization product was isolated in the final step of the synthesis of nevirapine, a non‐nucleoside inhibitor of HIV‐1 reverse transcriptase. Based on infrared spectrometry, mass spectrometry, and a number of two‐dimensional nmr experiments, the structure of this product was assigned to be 2‐((2′‐cyclopropylamino)‐3′‐pyridyl)‐7‐methyloxazolo[5,4‐ b ]pyridine, 9 . Results of a single crystal X‐ray analysis confirmed this structural assignment. This product arises from cyclization of N ‐(2‐chloro‐4‐methyl‐3‐pyridyl)‐2‐(cyclopropylamine)‐3‐pyridinecarboxamide, 8 , by displacement of the chlorine with the amide carbonyl oxygen. A competitive reaction occurs when 8 is deprotonated prior to cyclization to form nevirapine, 11‐cyclopropyl‐5,11‐dihydro‐4‐methyl‐6 H ‐dipyrido[3,2‐ b :2′,3′‐ e ][1,4]diazepin‐6‐one, 2 .