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Structural elucidation of an oxazolo[5,4‐ b ]pyridine: An alternative cyclization product related to nevirapine
Author(s) -
Norman Mark H.,
Minick Douglas J.,
Martin Gary E.
Publication year - 1993
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570300328
Subject(s) - chemistry , nevirapine , pyridine , stereochemistry , product (mathematics) , natural product , oxazole , combinatorial chemistry , organic chemistry , human immunodeficiency virus (hiv) , virology , viral load , antiretroviral therapy , geometry , mathematics , biology
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 .