瑞舒伐他汀钙有关物质的合成

Synthesis of the Related Substances of Rosuvastatin Calcium

为控制瑞舒伐他汀钙的质量,制备了瑞舒伐他汀钙的5个有关物质:[(3R,5S,E)-7-[4-(4-氟苯基)-2-[[2-[4-(4-氟苯基)-6-异丙基-2-[N-甲基(甲基磺酰胺基)]嘧啶-5-基]-2-羟基乙基]-N-甲基磺酰胺基]-6-异丙基嘧啶-5-基]-3,5-二羟基庚-6-烯酸酯]钙盐(有关物质A)、[(3R,5S,E)-7-[4-(4-氟苯基)-2-[[(E)-2-[4-(4-氟苯基)-6-异丙基-2-[N-甲基(甲基磺酰胺基)]嘧啶-5-基]乙烯基]-N-甲基磺酰胺基]-6-异丙基嘧啶-5-基]-3,5-二羟基庚-6-烯酸酯]钙盐(有关物质B)、N-[4-(4-氟苯基)-5-[(E)-2-[(2R,4R)-4-羟基-6-氧代四氢-2H-吡喃-2-基]乙烯基]-6-异丙基嘧啶-2-基]-N-甲基甲磺酰胺(有关物质C)、N-[(R)-8-氟-6-[(2S,4R)-4-羟基-6-氧代四氢-2H-吡喃-2-基]-4-异丙基-5,6-二氢苯并[h]-喹唑啉-2-基]-N-甲基甲磺酰胺(有关物质D)、N-[(S)-8-氟-6-[(2S,4R)-4-羟基-6-氧代四氢-2H-吡喃-2-基]-4-异丙基-5,6-二氢苯并[h]喹唑啉-2-基]-N-甲基甲磺酰胺(有关物质E),并通过MS、1H NMR和比旋度对结构进行了确证。

In order to control the quality of rosuvastatin calcium,five related substances of rosuvastatin calcium were synthesized:[(3R,5S,E)-7-[4-(4-fluorophenyl)-2-[[2-[4-(4-fluorophenyl)-6-isopropyl-2-[Nmethyl(methanesulfonamido)]pyrimidin-5-yl]-2-hydroxyethyl]-N-methylsulfonamido]-6-isopropylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate]calcium salt(related substance A),[(3R,5S,E)-7-[4-(4-fluorophenyl)-2-[[(E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-[N-methyl(methanesulfonamido)]pyrimidine-5-yl]vinyl]-N-methylsulfonamide]-6-isopropylpyrimidin-5-yl]-3,5-dihydroxyheptyl-6-enoate]calcium salt(related substance B),N-[4-(4-fluorophenyl)-5-[(E)-2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]vinyl]-6-isopropylpyrimidin-2-yl]-Nmethylmethanesulfonamide(related substance C),N-[(R)-8-fiuoro-6-[(2S,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]-4-isopropyl-5,6-dihydrobenzo[h]quinazolin-2-yl]-N-methylmethanesulfonamide(related substance D),and N-[(S)-8-fluoro-6-[(2S,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]-4-isopropyl-5,6-dihydrobenzo[h]quinazolin-2-yl]-Nmethylmethanesulfonamide(related substance E).And their structures were confirmed by MS,1H NMR and the optical rotation.