公开(公告)号：EP1826204A1

公开(公告)日：2007-08-29

申请号：EP06380038.7

申请日：2006-02-28

申请人： LABORATORIOS DEL DR. ESTEVE, S.A.

发明人： Torrens Jover, Antoni ,  Buschmann, Helmut Henrich ,  Dahmen, Stefan ,  Lormann, Matthias

IPC分类号： C07D333/12 ,  C07D333/14 ,  C07D333/24

CPC分类号： C07D333/24 ,  C07D333/12 ,  C07D333/14 ,  Y02P20/55

摘要： The present invention is directed to a process for the preparation of an enantiomerically enriched compound of formula II

wherein,
R 1 , R 2 and R 3 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 -CH 2 -OR 4 , -CH 2 -halogen or - CH 2 -NR 6 R 7 ;
wherein
Z is selected from -NR 6 R 7 or -OR 5 , wherein R 5 is selected from hydrogen, substituted or unsubstituted lower alkyl or ester activating group;
R 4 is selected from hydrogen, hydroxyl protecting group or hydroxyl activating group;
R 6 and R 7 are each independently selected from hydrogen, amino protecting group, amido protecting group or substituted or unsubstituted lower alkyl;

which comprises an enantioselective addition with a thienyl zinc reagent, in the presence of a chiral ligand.

摘要翻译： 本发明涉及一种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-CH 2 -OR 4，-CH 2 - 卤素或-CH 2 -NR 6 R 7; 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; R 4选自氢，羟基保护基或羟基活化基团; R 6和R 7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; 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：EP1671968A1

公开(公告)日：2006-06-21

申请号：EP04380265.1

申请日：2004-12-17

申请人： LABORATORIOS DEL DR. ESTEVE, S.A.

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

IPC分类号： C07D409/06

CPC分类号： C07D409/06

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

摘要翻译： 描述了制备（±）-2- [噻吩基（1-甲基-1H-吡唑-5-基）甲氧基] -N'-二甲基乙胺的前体醇的方法，通常用于甲烯基薁基乙氧基乙胺及其对映异构体。 它包括在手性配体的存在下将金属化的噻吩基试剂不对称加成到吡唑甲醛中以制备手性醇。 手性醇进一步O-烷基化以产生相应的药学活性的甲烯基吖唑烷氧基乙胺。

公开(公告)号：EP1671953A1

公开(公告)日：2006-06-21

申请号：EP04380266.9

申请日：2004-12-17

申请人： LABORATORIOS DEL DR. ESTEVE, S.A.

发明人： Torrens Jover, Antoni ,  Buschmann, Helmuth H. ,  Dahmen, Stefan ,  Lormann, Matthias

IPC分类号： C07D231/12

CPC分类号： C07D231/12

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

摘要翻译： 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，它包括 在手性配体存在下将金属化苯基试剂不对称地加成到吡唑甲醛中以制备手性醇。 手性醇进一步O-烷基化以得到西酞替尼或其对映异构体。