PROCESSO PARA A PREPARACAO DE 3S-¬¬4-¬¬4-(AMINOIMINOMETIL)FENIL|AMINO|-1,4-DIOXOBUTIL|AMINO|-4-PENTINOATO DE ETILO

• Main Authors: KATHLEEN THERESE MCLAUGHLIN, WENDELL W. DOUBLEDAY, VLASDISLAV ORLOVSKI, SOFYA TSYMBALOV, KEVIN A. BABIAK, JUNG M. PARK, MARK L. BOYS, BARNETT SYLVAIN PITZELE, SRINIVASAN BABU, DONALD W. MANSEN, JAMES R. BEHLING, GLENN L. STAHL, E. ANN HALLINAN, KIMBERLY J. CAIN-JANICKI, TIMOTHY JOSEPH HAGEN, DANIEL R. PILIPAUSKAS, JOHN R. MEDICH, DONALD E. KORTE, SEAN T. NUGENT, KAREN B. PETERSON, PAYMAN FARID
• Format: Patent
• Language: Portuguese
• Published: 29.09.2000
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY

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.