发明名称 |
Process for the preparation of derivatives of 1-(2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid |
摘要 |
The present invention relates to a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof:;wherein R represents one or more groups independently selected from fluorine, chlorine, bromine, and iodine,said process comprising the cyclopropanation of a compound of formula (II) with ethylene carbonate or ethylene sulfate:;wherein X is chlorine, bromine, iodine or a triflate group (CF3SO3) or a group;
wherein R is as defined above and G is —CN or —COOR2 wherein R2 is a C1-C4 straight or branched alkyl chain. |
申请公布号 |
US9290428(B2) |
申请公布日期 |
2016.03.22 |
申请号 |
US201414311630 |
申请日期 |
2014.06.23 |
申请人 |
CHIESI FARMACEUTICI S.p.A. |
发明人 |
Verzini Massimo;Cotarca Livius;Guidi Alberto;Melloni Alfonso;Maragni Paolo |
分类号 |
C07C51/09;C07C51/08;C07C67/343;C07C253/30;C07C67/22 |
主分类号 |
C07C51/09 |
代理机构 |
Oblon, McClelland, Maier & Neustadt, L.L.P. |
代理人 |
Oblon, McClelland, Maier & Neustadt, L.L.P. |
主权项 |
1. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof:wherein R represents one or more substituents independently selected from the group consisting of fluorine, chlorine, bromine, and iodine,
said process comprising: (i) reacting a compound of formula (II): wherein X is chlorine, bromine, iodine or a triflate group (CF3SO3) or a groupwherein R is as defined above, and G is —CN or —COOR2, wherein R2 is a C1-C4 straight or branched alkyl chain,
with a compound of formula (III):wherein Y is CO or SO2 in the presence of a base,
with the provisos that: (a) when Y is CO, then said reacting is carried out at a temperature of 120° C. to 180° C. and the molar ratio of said compound of formula (II) to said compound of formula (III) is 1:10 to 1:30 and said reacting is carried out in the presence of a compound able to complex an alkaline metal cation, said compound being selected from the group consisting of a polyethylene glycol, a phosphonium salt, and a crown ether; and (b) when G is —COOR2, then Y is SO2; to obtain a compound of formula (IV): wherein X and G are as defined above; (ii) when X is chlorine, bromine, iodine or a triflate group (CF3SO3), coupling said compound of formula (IV) with a compound of formula (V): wherein R is as defined above, to obtain a compound of formula (IV) wherein X is (iii) hydrolyzing said compound of formula (IV) wherein X isobtained in (i) or (ii), to obtain said compound of formula (I); and
(iv) optionally transforming said compound of formula (I) into a pharmaceutically acceptable salt thereof. |
地址 |
Parma IT |