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    PROCESS FOR THE PREPARATION OF N2-(1(S)-CARBOXY-3-PHENYLPROPYL);L-LYSYL-L-PROLINE
    14.
    发明专利
    PROCESS FOR THE PREPARATION OF N2-(1(S)-CARBOXY-3-PHENYLPROPYL);L-LYSYL-L-PROLINE 未知

    公开(公告)号：CA2311407A1

    公开(公告)日：2000-03-30

    申请号：CA2311407

    申请日：1999-09-22

    Applicant: KANEKA CORP

    Inventor： MOROSHIMA TADASHI ,  UEDA YASUYOSHI ,  FUSE YOSHIHIDE ,  YANAGIDA YOSHIFUMI

    IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02

    Abstract: A process for preparing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline (2) easily, efficiently and industrially advantageously, which comprises: the first step of conducting the alkaline hydrolysis of an N2-(1(S)-alkoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysyl-L-proline (1) by the use of n molar equivalents (wherein n 3) of an inorganic base per mol of the compound (1) either in a mixture of water with a hydrophilic organic solvent or in water; the second step of neutralizing the resulting reaction mixture with (n-1) to n molar equivalents (wherein n 3) of an inorganic acid, replacing the solvent system by a suitable one to thereby precipitate an inorganic salt formed by the above neutralization, and separating and removing the salt; and the third step of crystallizing the compound (2) present in the liquid mixture left after the above removal of the salt at its isoelectric point and recovering the compound (2) as a crystal, while salts mainly comprising organic acid salts resulting from trifluoroacetic acid remain dissolved in the mother liquor.

    15.
    发明专利
    未知

    公开(公告)号：DE69934084T2

    公开(公告)日：2007-04-05

    申请号：DE69934084

    申请日：1999-09-22

    Applicant: KANEKA CORP

    Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

    IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02 ,  C07K5/06

    Abstract: The process for producing N -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, which comprises: the first step of subjecting the N -(1(S)-alkoxycarbonyl-3-phenylpropyl)-N -trifluoroacetyl-L-lysyl -L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base in an amount of n molar equivalents (n >/= 3) per mole of the above compound (1), the second step of neutralizing the hydrolysis product using an inorganic acid in an amount of (n - 1) to n molar equivalents (n >/= 3) and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and the third step of causing the compound (2) existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the compound (2) in the form of crystals while retaining the salts comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.

    Process for the preparation of N2 -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline
    17.
    发明专利
    Process for the preparation of N2 -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline 未知

    公开(公告)号：CZ292494B6

    公开(公告)日：2003-10-15

    申请号：CZ20001897

    申请日：1999-09-22

    Applicant: KANEKA CORP

    Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

    IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02

    Abstract: The present invention relates to a process for the preparation of N2 -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, which comprises: the first step of subjecting the Ne2-(1(S)-alkoxycarbonyl-3-phenylpropyl)-Ne6-trifluorocetyl-L-lysyl-L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base, the second step of neutralizing the hydrolysis product using an inorganic acid and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and the third step of causing the final product existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the Ne2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in the form of crystals while retaining the salts comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.

    PROCESS FOR THE PREPARATION OF N-(1(S)-CARBOXY-3-PHENYLPROPYL)-L- LYSYL-L-PROLINE
    20.
    发明专利
    PROCESS FOR THE PREPARATION OF N-(1(S)-CARBOXY-3-PHENYLPROPYL)-L- LYSYL-L-PROLINE 未知

    公开(公告)号：SI20271A

    公开(公告)日：2000-12-31

    申请号：SI9920011

    申请日：1999-09-22

    Applicant: KANEKA CORP

    Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

    IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02

    Abstract: A process for preparing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline (2) easily, efficiently and industrially advantageously, which comprises: the first step of conducting the alkaline hydrolysis of an N2-(1(S)-alkoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysyl-L-proline (1) by the use of n molar equivalents (wherein n = 3) of an inorganic base per mol of the compound (1) either in a mixture of water with a hydrophilic organic solvent or in water; the second step of neutralizing the resulting reaction mixture with (n-1) to n molar equivalents (wherein n = 3) of an inorganic acid, replacing the solvent system by a suitable one to thereby precipitate an inorganic salt formed by the above neutralization, and separating and removing the salt; and the third step of crystallizing the compound (2) present in the liquid mixture left after the above removal of the salt at its isoelectric point and recovering the compound (2) as a crystal, while salts mainly comprising organic acid salts resulting from trifluoroacetic acid remain dissolved in the mother liquor.

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