Author(s): ZHANG Ya-ran, SHI Ying, LI Wei, ZHAO Xun-chen, DAO Shuo, CSPC Zhongqi Pharmaceutical Technology Co., Ltd.
Pages: 1143-1146
Year: 2014 Issue:  12
Journal: Chemical Reagents
Keyword:  antihyperlipidemics; rosuvastatin calcium; related substance; synthesis;
Abstract: To perform the quality control of antihyperlipidemics drug rosuvastatin calcium,three related substances of rosuvastatin calcium were prepared. Starting from rosuvastatin acid,the unreported stratagem was adopted to obtain( E)-7-{ 4-( 4-fluorophenyl)-6-isopropyl-2-[methyl( methylsulfonyl)amino] pyrimidin-5-yl }-( 3S,5S)-dihydroxyhept-6-enoic acid,calcium salt( 2∶ 1)( A) and N-{ 4-( 4-fluorophenyl)-5-[( E)-2-[( 2S,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl] vinyl ]-6-isopropylpyrimidin-2-yl }-N-methylmethanesulfonamide( B). Synthetic route of related substance A involving configuration inversion.( E)-7-{ 4-( 4-Fluorophenyl)-6-isopropyl-2-[methyl( methylsulfonyl) amino]pyrimidin-5-yl}-( 3S,5R)-dihydroxyhept-6-enoic acid,calcium salt( 2 ∶ 1)( C) was obtained by total synthesis. The structures were confirmed by1 HNMR and ESI-MS. These three related substances can be used as the reference substance of the impurities in the quality control of rosuvastatin calcium.