Patent ID: 6271393
Filing Date: 2001-08-07
Classification: A61P,C07K

Abstract:
A process for producing N2-(1(S)-carboxy-3-phenylpropyl) L-lysyl-L-proline of the formula (2):##STR6##from an N2- (1(S)-alkoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl L-lysyl-L-proline of the general formula (1):##STR7##wherein R represents an alkyl group,which comprises:the first step: subjecting the N2-(1(S)-alkoxycarbonyl 3-phenylpropyl) -N6-trifluoroacetyl-L-lysyl-L-proline (1) to alkali hydrolysis in a solvent system being selected from among a mixed solution composed of water and a hydrophilic organic solvent, and water using an inorganic base in an amount of n molar equivalents (n .gtoreq. 3) per mole of the above compound (1),the second step: neutralizing the hydrolysis product using an inorganic acid in an amount of (n - 1) to n molar equivalents (n .gtoreq. 3) andseparating and removing the inorganic salt formed from the above inorganic base and inorganic acid in the reaction mixture by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt,said solvent system being selected from a hydrophilic organic solvent, a mixed solvent composed of water and a hydrophilic organic solvent, and water, andthe third step: causing the N2-(1(S)-carboxy-3-phenylpropyl) L-lysyl-L-proline (2) existing in the mixture after removal of the inorganic salt to crystallize out from a solvent system at the isoelectric point thereof,said solvent system being selected from a hydrophilic organic solvent, a mixed solvent composed of water and a hydrophilic organic solvent, and water, andthereby recovering the N2- (1(S)-carboxy-3-phenylpropyl) L-lysyl-L-proline (2) in the form of crystals while retaining the salts mainly comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.