A Scaleable Synthesis of Methyl 3-Amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate

A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (1b), starting from 5-bromo-2-methoxypyridine (8) and 4-fluorobenzaldehyde (9), is described. Key steps in the process include lithium–bromine exchange of 8, addition of the resulting lithiate to aldehyde 9, regioselect...

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Published inOrganic process research & development Vol. 11; no. 5; pp. 899 - 902
Main Authors Boros, Eric E, Burova, Svetlana A, Erickson, Greg A, Johns, Brian A, Koble, Cecilia S, Kurose, Noriyuki, Sharp, Matthew J, Tabet, Elie A, Thompson, James B, Toczko, Matthew A
Format Journal Article
LanguageEnglish
Published American Chemical Society 01.09.2007
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Summary:A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (1b), starting from 5-bromo-2-methoxypyridine (8) and 4-fluorobenzaldehyde (9), is described. Key steps in the process include lithium–bromine exchange of 8, addition of the resulting lithiate to aldehyde 9, regioselective nitration of pyridone 12, and Pd-catalyzed alkoxycarbonylation of bromopyridine 15b. Overall yield of the five-stage synthesis was 23%; intermediates 10, 12, 13, 15b, and final product 1b·HCl were isolated as filterable solids. Compounds 1a,b are important intermediates in the synthesis of 7-benzylnaphthyridinones (e.g., 2) and related HIV-1 integrase inhibitors.
ISSN:1083-6160
1520-586X
DOI:10.1021/op7001326