Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist

Robert D. Larsen; Anthony O. King; Cheng Y. Chen; Edward G. Corley; Bruce S. Foster; F. Edward Roberts; Chunhua Yang; David R. Lieberman; Robert A. Reamer; David M. Tschaen; Thomas R. Verhoeven; Paul J. Reider; S. Lo Young; Lucius T. Rossano; Sidney Brookes; David Meloni; James R. Moore; John F. Arnett

doi:10.1021/jo00100a048

Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist

Robert D. Larsen, Anthony O. King, Cheng Y. Chen, Edward G. Corley, Bruce S. Foster, F. Edward Roberts, Chunhua Yang, David R. Lieberman, Robert A. Reamer, David M. Tschaen, Thomas R. Verhoeven, Paul J. Reider, S. Lo Young, Lucius T. Rossano, Sidney Brookes, David Meloni, James R. Moore, John F. Arnett

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186 Scopus citations

Abstract

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-phenyltetrazole 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.

Original language	English (US)
Pages (from-to)	6391-6394
Number of pages	4
Journal	Journal of Organic Chemistry
Volume	59
Issue number	21
DOIs	https://doi.org/10.1021/jo00100a048
State	Published - Oct 1 1994
Externally published	Yes

All Science Journal Classification (ASJC) codes

Organic Chemistry

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Larsen, R. D., King, A. O., Chen, C. Y., Corley, E. G., Foster, B. S., Roberts, F. E., Yang, C., Lieberman, D. R., Reamer, R. A., Tschaen, D. M., Verhoeven, T. R., Reider, P. J., Young, S. L., Rossano, L. T., Brookes, S., Meloni, D., Moore, J. R., & Arnett, J. F. (1994). Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist. Journal of Organic Chemistry, 59(21), 6391-6394. https://doi.org/10.1021/jo00100a048

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title = "Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist",

abstract = "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-phenyltetrazole 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.",

author = "Larsen, {Robert D.} and King, {Anthony O.} and Chen, {Cheng Y.} and Corley, {Edward G.} and Foster, {Bruce S.} and Roberts, {F. Edward} and Chunhua Yang and Lieberman, {David R.} and Reamer, {Robert A.} and Tschaen, {David M.} and Verhoeven, {Thomas R.} and Reider, {Paul J.} and Young, {S. Lo} and Rossano, {Lucius T.} and Sidney Brookes and David Meloni and Moore, {James R.} and Arnett, {John F.}",

year = "1994",

month = oct,

day = "1",

doi = "10.1021/jo00100a048",

language = "English (US)",

volume = "59",

pages = "6391--6394",

journal = "Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society",

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Larsen, RD, King, AO, Chen, CY, Corley, EG, Foster, BS, Roberts, FE, Yang, C, Lieberman, DR, Reamer, RA, Tschaen, DM, Verhoeven, TR, Reider, PJ, Young, SL, Rossano, LT, Brookes, S, Meloni, D, Moore, JR & Arnett, JF 1994, 'Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist', Journal of Organic Chemistry, vol. 59, no. 21, pp. 6391-6394. https://doi.org/10.1021/jo00100a048

TY - JOUR

T1 - Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist

AU - Larsen, Robert D.

AU - King, Anthony O.

AU - Chen, Cheng Y.

AU - Corley, Edward G.

AU - Foster, Bruce S.

AU - Roberts, F. Edward

AU - Yang, Chunhua

AU - Lieberman, David R.

AU - Reamer, Robert A.

AU - Tschaen, David M.

AU - Verhoeven, Thomas R.

AU - Reider, Paul J.

AU - Young, S. Lo

AU - Rossano, Lucius T.

AU - Brookes, Sidney

AU - Meloni, David

AU - Moore, James R.

AU - Arnett, John F.

PY - 1994/10/1

Y1 - 1994/10/1

N2 - 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-phenyltetrazole 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.

AB - 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-phenyltetrazole 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.

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DO - 10.1021/jo00100a048

M3 - Article

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JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 21

ER -

Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist

Abstract

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