公开(公告)号：US07078531B2

公开(公告)日：2006-07-18

申请号：US11041638

申请日：2005-01-24

Applicant: Antoni Torrens Jover ,  Helmut H. Buschmann ,  Stefan Dahmen ,  Matthias Lormann

Inventor： Antoni Torrens Jover ,  Helmut H. Buschmann ,  Stefan Dahmen ,  Matthias Lormann

IPC: C07D231/12

CPC classification number: C07D409/06

Abstract: A process is described for the preparation of a precursor alcohol of (±)-2-[thienyl(1-methyl-1H-pyrazol-5-yl)methoxy]-N,N-dimethyletanamine and in general for thienylazolylalcoxyethanamines and their enantiomers. The process involves asymmetric addition of a metalated thienyl reagent to a pyrazolcarbaldehyde in the presence of a chiral ligand to yield chiral alcohols. The chiral alcohols are further O-alkylated to yield the corresponding pharmaceutically active thienylazolylalcoxyethanamines.

Abstract translation: 描述了制备（±）-2- [噻吩基（1-甲基-1H-吡唑-5-基）甲氧基] -N，N-二甲基乙胺的前体醇的方法，通常用于噻吩并噻唑基醛乙氧基胺及其对映异构体。 该方法包括在手性配体的存在下将金属化噻吩试剂不对称加成到吡唑甲醛中以产生手性醇。 手性醇进一步O-烷基化，得到相应的药学活性噻吩并噻唑基乙醇胺。

公开(公告)号：US07109349B2

公开(公告)日：2006-09-19

申请号：US11041637

申请日：2005-01-24

Applicant: Antoni Torrens Jover ,  Helmut H. Buschmann ,  Stefan Dahmen ,  Matthias Lormann

Inventor： Antoni Torrens Jover ,  Helmut H. Buschmann ,  Stefan Dahmen ,  Matthias Lormann

IPC: C07D231/12

CPC classification number: C07D231/12

Abstract: A process is described for the preparation of a precursor alcohol of Cizolirtine, (±)-2-[phenyl(1-methyl-1H-pyrazol-5-yl)methoxy]-N,N-dimethylethanamine and its enantiomers. The process involves the asymmetric addition of a metalated phenyl reagent to a pyrazolcarbaldehyde in the presence of a chiral ligand to yield chiral alcohols. The chiral alcohols are further O-alkylated to yield Cizolirtine or its enantiomers.

Abstract translation: 描述了制备Cizolirtine（±）-2- [苯基（1-甲基-1H-吡唑-5-基）甲氧基] -N，N-二甲基乙胺及其对映异构体的前体醇的方法。 该方法包括在手性配体存在下将金属化苯基试剂不对称加成到吡唑甲醛中以产生手性醇。 手性醇进一步O-烷基化以得到西来甜胺或其对映异构体。

公开(公告)号：US20060135787A1

公开(公告)日：2006-06-22

申请号：US11041638

申请日：2005-01-24

Applicant: Antoni Jover ,  Helmut Buschmann ,  Stefan Dahmen ,  Matthias Lormann

Inventor： Antoni Jover ,  Helmut Buschmann ,  Stefan Dahmen ,  Matthias Lormann

IPC: C07D409/02

CPC classification number: C07D409/06

Abstract: A process is described for the preparation of a precursor alcohol of (±)-2-[thienyl(1-methyl-1H-pyrazol-5-yl)methoxy]-N,N-dimethyletanamine and in general for thienylazolylalcoxyethanamines and their enantiomers. The process involves asymmetric addition of a metalated thienyl reagent to a pyrazolcarbaldehyde in the presence of a chiral ligand to yield chiral alcohols. The chiral alcohols are further O-alkylated to yield the corresponding pharmaceutically active thienylazolylalcoxyethanamines.

Abstract translation: 描述了制备（±）-2- [噻吩基（1-甲基-1H-吡唑-5-基）甲氧基] -N，N-二甲基乙胺的前体醇的方法，通常用于噻吩并噻唑基醛乙氧基胺及其对映异构体。 该方法包括在手性配体的存在下将金属化噻吩试剂不对称加成到吡唑甲醛中以产生手性醇。 手性醇进一步O-烷基化，得到相应的药学活性噻吩并噻唑基乙醇胺。

公开(公告)号：US20090247771A1

公开(公告)日：2009-10-01

申请号：US12280084

申请日：2007-02-27

Applicant: Helmut Heinrich Buschmann ,  Antoni Torrens Jover ,  Matthias Lormann ,  Stefan Dahmen

Inventor： Helmut Heinrich Buschmann ,  Antoni Torrens Jover ,  Matthias Lormann ,  Stefan Dahmen

IPC: C07D333/16

CPC classification number: C07D333/24 ,  C07D333/12 ,  C07D333/14 ,  Y02P20/55

Abstract: The present invention is directed to a process for the preparation of an enantiomerically enriched compound of formula II wherein, R1, R2 and R3 are each independently selected from hydrogen, halogen, substituted or unsubstituted lower alkyl or substituted or unsubstituted aryl; X is —C(═O)-Z or —Y, wherein —Y is selected from —CH2—OR4, —CH2-halogen or —CH2—NR6R7; wherein Z is selected from —NR6R7 or —OR5, wherein R5 is selected from hydrogen, substituted or unsubstituted lower alkyl or ester activating group; R4 is selected from hydrogen, hydroxyl protecting group or hydroxyl activating group; R6 and R7 are each independently selected from hydrogen, amino protecting group, amido protecting group or substituted or unsubstituted lower alkyl; or a pharmaceutically acceptable salt, complex or solvate thereof; which comprises an enantioselective addition with a thienyl zinc reagent, in the presence of a chiral ligand.

Abstract translation: 本发明涉及制备对映体富集的式II化合物的方法，其中R 1，R 2和R 3各自独立地选自氢，卤素，取代或未取代的低级烷基或取代或未取代的芳基; X是-C（-O）-Z或-Y，其中-Y选自-CH2-OR4，-CH2-卤素或-CH2-NR6R7; 其中Z选自-NR 6 R 7或-OR 5，其中R 5选自氢，取代或未取代的低级烷基或酯活化基团; R4选自氢，羟基保护基或羟基活化基团; R6和R7各自独立地选自氢，氨基保护基，酰氨基保护基或取代或未取代的低级烷基; 或其药学上可接受的盐，复合物或溶剂化物; 其包括在手性配体存在下用噻吩锌试剂进行对映选择性加成。

公开(公告)号：US20060135788A1

公开(公告)日：2006-06-22

申请号：US11041637

申请日：2005-01-24

Applicant: Antoni Jover ,  Helmut Buschmann ,  Stefan Dahmen ,  Matthias Lormann

Inventor： Antoni Jover ,  Helmut Buschmann ,  Stefan Dahmen ,  Matthias Lormann

IPC: C07D231/12

CPC classification number: C07D231/12

Abstract: A process is described for the preparation of a precursor alcohol of Cizolirtine, (±)-2-[phenyl(1-methyl-1H-pyrazol-5-yl)methoxy]-N,N-dimethylethanamine and its enantiomers. The process involves the asymmetric addition of a metalated phenyl reagent to a pyrazolcarbaldehyde in the presence of a chiral ligand to yield chiral alcohols. The chiral alcohols are further O-alkylated to yield Cizolirtine or its enantiomers.

Abstract translation: 描述了制备Cizolirtine（±）-2- [苯基（1-甲基-1H-吡唑-5-基）甲氧基] -N，N-二甲基乙胺及其对映异构体的前体醇的方法。 该方法包括在手性配体存在下将金属化苯基试剂不对称加成到吡唑甲醛中以产生手性醇。 手性醇进一步O-烷基化以得到西来甜胺或其对映异构体。