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 a is deprotonated prior to cyclization to form nevirapine, 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one, 2.