Title:
【発明の名称】エチル3S-〔〔4-〔〔4-(アミノイミノメチル)フェニル〕アミノ〕-1,4-ジオキソブチル〕アミノ〕-4-ペンチノエートの製造法
Document Type and Number:
Japanese Patent JPH11509208
Kind Code:
A
Abstract:
The present invention relates to a novel process for the preparation of ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoate and pharmaceutically acceptable acid addition salt thereof which comprises treating (trimethylsilyl)acetylene sequentially with n-butyllithium and 4-formylmorpholine followed by acid hydrolysis to give 3-(trimethylsilyl)-2-propynal; treating 3-(trimethylsilyl)-2-propynal with lithium bis(trimethylsilyl)amide to give in situ N,3-bis(trimethylsilyl)-2-propyn-1-imine; condensation of N,3-bis(trimethylsilyl)-2-propyn-1-imine with lithium t-butyl acetate to give (+/-)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate; treating (+/-)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate- with p-toluenesulfonic acid to give (+/-)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate, mono p-toluenesulfonic acid salt, treatment of resulting salt with ethanol in the presence of p-toluenesulfonic acid to give (+/-)ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate; desilylation of (+/-)ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate to give in situ (+/-)ethyl 3-amino-4-pentynoate; resolution of (+/-)ethyl 3-amino-4-pentynoate using (R)-(-)-mandelic acid and treatment of the resolved product with gaseous hydrochloric acid to give ethyl 3S-amino-4-pentynoate, monohydrochloride; coupling the ethyl 3S-amino-4-pentynoate, monohydrochloride to 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid, monohydrochloride in the presence of isobutyl chloroformate and N-methylmorpholine to give ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoate, monohydrochloride.
Inventors:
Babiak, Kevin A.
Bab, Srinivasan
Bering, James Earl.
Boyz, Mark Elle.
Kane-Janikey, Kimberley Jay.
Doubleday, Wendell W.
Farid, Payman
Hagen, Timothy Jay.
Harinan, E. Ann
Hansen, Donald W., Jr.
Cote, Donald E.
McCrawlin, Kathleen Tea.
Medici, John Earl.
New Junt, Scene Tee.
Orlovsky, Brass dislove
Park, Jung M.
Peterson, Karen Bee.
Piripauscus, Daniel Earl.
Pizzere, Barnet S.
Tosim Barob, Sofia
Stahl, Glen Elle.
Bab, Srinivasan
Bering, James Earl.
Boyz, Mark Elle.
Kane-Janikey, Kimberley Jay.
Doubleday, Wendell W.
Farid, Payman
Hagen, Timothy Jay.
Harinan, E. Ann
Hansen, Donald W., Jr.
Cote, Donald E.
McCrawlin, Kathleen Tea.
Medici, John Earl.
New Junt, Scene Tee.
Orlovsky, Brass dislove
Park, Jung M.
Peterson, Karen Bee.
Piripauscus, Daniel Earl.
Pizzere, Barnet S.
Tosim Barob, Sofia
Stahl, Glen Elle.
Application Number:
JP50606097A
Publication Date:
August 17, 1999
Filing Date:
July 12, 1996
Export Citation:
Assignee:
G.D.Searle & Company
International Classes:
C07C227/02; C07B61/00; C07C227/12; C07C227/34; C07C229/08; C07C257/18; (IPC1-7): C07C257/18
Attorney, Agent or Firm:
Akira Asamura (3 outside)
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