Development of a scaleable process for the synthesis of a next-generation statin

Lindsay A. Hobson; Otute Akiti; Subodh S. Deshmukh; Shannon Harper; Kishta Katipally; Chiajen J. Lai; Robert C. Livingston; Ehrlic Lo; Michael M. Miller; Srividya Ramakrishnan; Lifen Shen; Jan Spink; Srinivas Tummala; Chenkou Wei; Kana Yamamoto; John Young; Rodney L. Parsons

doi:10.1021/op100010n

Development of a scaleable process for the synthesis of a next-generation statin

Lindsay A. Hobson, Otute Akiti, Subodh S. Deshmukh, Shannon Harper, Kishta Katipally, Chiajen J. Lai, Robert C. Livingston, Ehrlic Lo, Michael M. Miller, Srividya Ramakrishnan, Lifen Shen, Jan Spink, Srinivas Tummala, Chenkou Wei, Kana Yamamoto, John Young, Rodney L. Parsons

国際理工学センター（理工学術院）

研究成果: Article

19 引用（Scopus）

抜粋

This manuscript details the process research and development of a convergent and safe approach to 1 on a multikilo scale. Specific highlights of the process development efforts will be described, including the development of a dehydrogenation method for dihydropyrimidines and a thermochemically safe synthesis of a 1,2,4-aminotriazole fragment. A key feature of the synthesis is the use and optimization of a modified Julia-Kocienski olefination reaction. Specifically, we report an unprecedented dependence of the product olefin geometry on reaction temperature, where an E:Z ratio as high as 200:1 can be obtained. Initial insights into the mechanistic rationale for this observation are also provided. Finally, a purity upgrade sequence via an intermediate crystalline form is highlighted as a method of controlling the final API quality.

元の言語	English
ページ（範囲）	441-458
ページ数	18
ジャーナル	Organic Process Research and Development
巻	14
発行部数	2
DOI	https://doi.org/10.1021/op100010n
出版物ステータス	Published - 2010 3 19

フィンガープリント

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

これを引用

Hobson, L. A., Akiti, O., Deshmukh, S. S., Harper, S., Katipally, K., Lai, C. J., Livingston, R. C., Lo, E., Miller, M. M., Ramakrishnan, S., Shen, L., Spink, J., Tummala, S., Wei, C., Yamamoto, K., Young, J., & Parsons, R. L. (2010). Development of a scaleable process for the synthesis of a next-generation statin. Organic Process Research and Development, 14(2), 441-458. https://doi.org/10.1021/op100010n

Development of a scaleable process for the synthesis of a next-generation statin. / Hobson, Lindsay A.; Akiti, Otute; Deshmukh, Subodh S.; Harper, Shannon; Katipally, Kishta; Lai, Chiajen J.; Livingston, Robert C.; Lo, Ehrlic; Miller, Michael M.; Ramakrishnan, Srividya; Shen, Lifen; Spink, Jan; Tummala, Srinivas; Wei, Chenkou; Yamamoto, Kana; Young, John; Parsons, Rodney L.

：: Organic Process Research and Development, 巻 14, 番号 2, 19.03.2010, p. 441-458.

研究成果: Article

Hobson, LA, Akiti, O, Deshmukh, SS, Harper, S, Katipally, K, Lai, CJ, Livingston, RC, Lo, E, Miller, MM, Ramakrishnan, S, Shen, L, Spink, J, Tummala, S, Wei, C, Yamamoto, K, Young, J & Parsons, RL 2010, 'Development of a scaleable process for the synthesis of a next-generation statin', Organic Process Research and Development, 巻. 14, 番号 2, pp. 441-458. https://doi.org/10.1021/op100010n

Hobson, Lindsay A. ; Akiti, Otute ; Deshmukh, Subodh S. ; Harper, Shannon ; Katipally, Kishta ; Lai, Chiajen J. ; Livingston, Robert C. ; Lo, Ehrlic ; Miller, Michael M. ; Ramakrishnan, Srividya ; Shen, Lifen ; Spink, Jan ; Tummala, Srinivas ; Wei, Chenkou ; Yamamoto, Kana ; Young, John ; Parsons, Rodney L. / Development of a scaleable process for the synthesis of a next-generation statin. ：: Organic Process Research and Development. 2010 ; 巻 14, 番号 2. pp. 441-458.

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AU - Lai, Chiajen J.

AU - Livingston, Robert C.

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AU - Miller, Michael M.

AU - Ramakrishnan, Srividya

AU - Shen, Lifen

AU - Spink, Jan

AU - Tummala, Srinivas

AU - Wei, Chenkou

AU - Yamamoto, Kana

AU - Young, John

AU - Parsons, Rodney L.

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文献にアクセス

10.1021/op100010n