Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist

A highly efficient, convergent approach to the synthesis of the angiotensin II receptor antagonist losartan (1) is described. Directed ortho-metalation of 2-trityl-5-phenyltetraz ole provides the key boronic acid intermediate 10 for palladium-catalyzed biaryl coupling with bromide 5 obtained from th...

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Published inJournal of organic chemistry Vol. 59; no. 21; pp. 6391 - 6394
Main Authors Larsen, Robert D, King, Anthony O, Chen, Cheng Y, Corley, Edward G, Foster, Bruce S, Roberts, F. Edward, Yang, Chunhua, Lieberman, David R, Reamer, Robert A, Tschaen, David M, Verhoeven, Thomas R, Reider, Paul J, Lo, Young S, Rossano, Lucius T, Brookes, A. Sidney, Meloni, David, Moore, James R, Arnett, John F
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 01.10.1994
American ChemicalSociety
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
CARBON BOND FORMATION
ANTIHYPERTENSIVES
CROSS-COUPLING REACTIONS
POTENT
DIRECTED ORTHO-METALATION
ARYL HALIDES
CONNECTIONS
DERIVATIVES
DISCOVERY
UNSYMMETRICAL BIARYLS
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Summary:A highly efficient, convergent approach to the synthesis of the angiotensin II receptor antagonist losartan (1) is described. Directed ortho-metalation of 2-trityl-5-phenyltetraz ole provides the key boronic acid intermediate 10 for palladium-catalyzed biaryl coupling with bromide 5 obtained from the regioselective alkylation of the chloroimidazole 2. This methodology overcomes many of the drawbacks associated with previously reported syntheses.
Bibliography:istex:A9FDA262987C92FDD1E4666A6E2E81616E7C160B
ark:/67375/TPS-0SC2WPT7-L
ISSN:0022-3263
1520-6904
DOI:10.1021/jo00100a048