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

Research output: Contribution to journal › Article › peer-review

208 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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10.1021/jo00100a048

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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

@article{19dc196b9f8b4a40a4428d88b629bde5,

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",

number = "21",

}

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.

UR - https://www.scopus.com/pages/publications/0028054343

UR - https://www.scopus.com/pages/publications/0028054343#tab=citedBy

U2 - 10.1021/jo00100a048

DO - 10.1021/jo00100a048

M3 - Article

AN - SCOPUS:0028054343

SN - 0022-3263

VL - 59

SP - 6391

EP - 6394

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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