4-Pentynoic acid, 3-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-, ethyl ester, monohydrochloride, (3S)-

Originator

Complamin,Doetsch Grether AG

Uses

Prevention of post-recanalization reocclusion of coronary vessels; treatment of unstable angina.

Manufacturing Process

4-Aminobenzamidine dihydrochloride (25.0 g, 120 mmol), was added to dry DMF (100 ml). To this solution dry pyridine (100 ml) and succinic anhydride (12.0 g, 120 mmol) followed by dimethylaminopyridine (DMAP 1.5 g 0.012 mmol) were added. The product precipitated after heating for 0.5 h at 100°C, then was filtered, washed with water, acetonitrile and ether. The light solid was suspended in dioxane, 4 N HCl in dioxane (100 ml) was added and the suspension was stirred for 1 h, filtered and dried in a desiccator to give 28.0 g, 88% of 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxo-butanoic acid hydrochloride as a white yellow solid, melting point 270-290°C (dec.).
4-[[4-(Aminoiminomethyl)phenyl]amino]-4-oxo-butanoic acid hydrochloride was added to dry DMF followed by N-methylmorpholine and isobutyl chloroformate at 25°C. The mixture was stirred for 5 min. Ethyl 3-amino-4- pentynoate was added followed by di-iso-propylethylamine and a catalytic amount of dimethylaminopyridine. After 1 h, the solvent was removed under reduced pressure and the product was purified by reverse phase chromatography (0.05% TFA water/acetonitrile) and lyophilized to give ethyl 3-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4- pentynoate.
By division of stereo-isomers of the ethyl 3-[[4-[[4-(aminoiminomethyl) phenyl]amino]-1,4-dioxobutyl]amino]-4-pentynoate on column chromatography the ethyl (3S)-3-[[4-[[4-(aminoiminomethyl)phenyl]amino]- 1,4-dioxobutyl]amino]-4-pentynoate may be obtained.

Therapeutic Function

Fibrinogen receptor antagonist