Pilot-plant preparation of an αvβ3 integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling

Jerry D. Clark; D. Keith Anderson; David V. Banaszak; Derek B. Brown; Ann M. Czyzewski; Albert D. Edeny; Puneh S. Forouzi; Donald J. Gallagher; V. H. Iskos; H. Peter Kleine; Carl M. Knable; Melissa K. Lantz; Mark A. Lapack; Christine M.V. Moore; Frank W. Muellner; James B. Murphy; Carlos A. Orihuela; Mark A. Pietz; Thomas E. Rogers; Peter G. Ruminski; Harish K. Santhanam; Tobin C. Schilke; Ajit S. Shah; Ahmad Y. Sheikh; Gerald A. Weisenburger; Bruce E. Wise

doi:10.1021/op900173f

Pilot-plant preparation of an α_vβ₃ integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling

Jerry D. Clark
, D. Keith Anderson
, David V. Banaszak
, Derek B. Brown
, Ann M. Czyzewski
, Albert D. Edeny
, Puneh S. Forouzi
, Donald J. Gallagher
, V. H. Iskos
, H. Peter Kleine
, Carl M. Knable
, Melissa K. Lantz
, Mark A. Lapack
, Christine M.V. Moore
, Frank W. Muellner
, James B. Murphy
, Carlos A. Orihuela
, Mark A. Pietz
, Thomas E. Rogers
, Peter G. Ruminski

Harish K. Santhanam, Tobin C. Schilke, Ajit S. Shah, Ahmad Y. Sheikh, Gerald A. Weisenburger, Bruce E. Wise

Section of Stem Cell Biology

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

4 Scopus citations

Abstract

Studies directed toward the process research, development, and scale-up preparation of the potential α_vβ₃ integrin antagonist 1 are described. A convergent approach is detailed wherein tetrahydropyrimidine hydroxybenzoic acid 2 is linked to the β-amino acid ester 3 via a diisoproylcarbodiimide, catalytic HOBt coupling reaction. Saponification of the resulting ethyl ester, isolation of the corresponding zwitterion, H₃PO₄ salt formation, crystallization, and acetonitrile-to-acetone exchange give rise to 1 as a crystalline monohydrate in 67% overall yield from 4.

Original language	English
Pages (from-to)	1088-1093
Number of pages	6
Journal	Organic Process Research and Development
Volume	13
Issue number	6
DOIs	https://doi.org/10.1021/op900173f
State	Published - Nov 20 2009

Access to Document

10.1021/op900173f

Cite this

Clark, J. D., Anderson, D. K., Banaszak, D. V., Brown, D. B., Czyzewski, A. M., Edeny, A. D., Forouzi, P. S., Gallagher, D. J., Iskos, V. H., Kleine, H. P., Knable, C. M., Lantz, M. K., Lapack, M. A., Moore, C. M. V., Muellner, F. W., Murphy, J. B., Orihuela, C. A., Pietz, M. A., Rogers, T. E., ... Wise, B. E. (2009). Pilot-plant preparation of an α_vβ₃ integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling. Organic Process Research and Development, 13(6), 1088-1093. https://doi.org/10.1021/op900173f

@article{97f5a58a83824b929b2fabd385a98f73,

title = "Pilot-plant preparation of an αvβ3 integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling",

abstract = "Studies directed toward the process research, development, and scale-up preparation of the potential αvβ3 integrin antagonist 1 are described. A convergent approach is detailed wherein tetrahydropyrimidine hydroxybenzoic acid 2 is linked to the β-amino acid ester 3 via a diisoproylcarbodiimide, catalytic HOBt coupling reaction. Saponification of the resulting ethyl ester, isolation of the corresponding zwitterion, H3PO4 salt formation, crystallization, and acetonitrile-to-acetone exchange give rise to 1 as a crystalline monohydrate in 67\% overall yield from 4.",

author = "Clark, \{Jerry D.\} and Anderson, \{D. Keith\} and Banaszak, \{David V.\} and Brown, \{Derek B.\} and Czyzewski, \{Ann M.\} and Edeny, \{Albert D.\} and Forouzi, \{Puneh S.\} and Gallagher, \{Donald J.\} and Iskos, \{V. H.\} and Kleine, \{H. Peter\} and Knable, \{Carl M.\} and Lantz, \{Melissa K.\} and Lapack, \{Mark A.\} and Moore, \{Christine M.V.\} and Muellner, \{Frank W.\} and Murphy, \{James B.\} and Orihuela, \{Carlos A.\} and Pietz, \{Mark A.\} and Rogers, \{Thomas E.\} and Ruminski, \{Peter G.\} and Santhanam, \{Harish K.\} and Schilke, \{Tobin C.\} and Shah, \{Ajit S.\} and Sheikh, \{Ahmad Y.\} and Weisenburger, \{Gerald A.\} and Wise, \{Bruce E.\}",

year = "2009",

month = nov,

day = "20",

doi = "10.1021/op900173f",

language = "English",

volume = "13",

pages = "1088--1093",

journal = "Organic Process Research and Development",

issn = "1083-6160",

number = "6",

}

Clark, JD, Anderson, DK, Banaszak, DV, Brown, DB, Czyzewski, AM, Edeny, AD, Forouzi, PS, Gallagher, DJ, Iskos, VH, Kleine, HP, Knable, CM, Lantz, MK, Lapack, MA, Moore, CMV, Muellner, FW, Murphy, JB, Orihuela, CA, Pietz, MA, Rogers, TE, Ruminski, PG, Santhanam, HK, Schilke, TC, Shah, AS, Sheikh, AY, Weisenburger, GA & Wise, BE 2009, 'Pilot-plant preparation of an α_vβ₃ integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling', Organic Process Research and Development, vol. 13, no. 6, pp. 1088-1093. https://doi.org/10.1021/op900173f

Pilot-plant preparation of an α_vβ₃ integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling. / Clark, Jerry D.; Anderson, D. Keith; Banaszak, David V. et al.
In: Organic Process Research and Development, Vol. 13, No. 6, 20.11.2009, p. 1088-1093.

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

TY - JOUR

T1 - Pilot-plant preparation of an αvβ3 integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling

AU - Clark, Jerry D.

AU - Anderson, D. Keith

AU - Banaszak, David V.

AU - Brown, Derek B.

AU - Czyzewski, Ann M.

AU - Edeny, Albert D.

AU - Forouzi, Puneh S.

AU - Gallagher, Donald J.

AU - Iskos, V. H.

AU - Kleine, H. Peter

AU - Knable, Carl M.

AU - Lantz, Melissa K.

AU - Lapack, Mark A.

AU - Moore, Christine M.V.

AU - Muellner, Frank W.

AU - Murphy, James B.

AU - Orihuela, Carlos A.

AU - Pietz, Mark A.

AU - Rogers, Thomas E.

AU - Ruminski, Peter G.

AU - Santhanam, Harish K.

AU - Schilke, Tobin C.

AU - Shah, Ajit S.

AU - Sheikh, Ahmad Y.

AU - Weisenburger, Gerald A.

AU - Wise, Bruce E.

PY - 2009/11/20

Y1 - 2009/11/20

N2 - Studies directed toward the process research, development, and scale-up preparation of the potential αvβ3 integrin antagonist 1 are described. A convergent approach is detailed wherein tetrahydropyrimidine hydroxybenzoic acid 2 is linked to the β-amino acid ester 3 via a diisoproylcarbodiimide, catalytic HOBt coupling reaction. Saponification of the resulting ethyl ester, isolation of the corresponding zwitterion, H3PO4 salt formation, crystallization, and acetonitrile-to-acetone exchange give rise to 1 as a crystalline monohydrate in 67% overall yield from 4.

AB - Studies directed toward the process research, development, and scale-up preparation of the potential αvβ3 integrin antagonist 1 are described. A convergent approach is detailed wherein tetrahydropyrimidine hydroxybenzoic acid 2 is linked to the β-amino acid ester 3 via a diisoproylcarbodiimide, catalytic HOBt coupling reaction. Saponification of the resulting ethyl ester, isolation of the corresponding zwitterion, H3PO4 salt formation, crystallization, and acetonitrile-to-acetone exchange give rise to 1 as a crystalline monohydrate in 67% overall yield from 4.

UR - https://www.scopus.com/pages/publications/72449205095

U2 - 10.1021/op900173f

DO - 10.1021/op900173f

M3 - Article

AN - SCOPUS:72449205095

SN - 1083-6160

VL - 13

SP - 1088

EP - 1093

JO - Organic Process Research and Development

JF - Organic Process Research and Development

IS - 6

ER -

Pilot-plant preparation of an α_vβ₃ integrin antagonist. Part 3. Process research and development of a diisopropylcarbodiimide and catalytic 1-hydroxybenzotriazole peptide coupling

Abstract

Access to Document

Other files and links

Fingerprint

Cite this