非洛地平原药中相关杂质的合成

Synthesis of Impurities in Bulk Drugs Felodipine

根据杂质产生的机理,模拟杂质产生的条件,合成了欧盟药典7.8所载非洛地平的3种杂质——2,6-二甲基-4-（2,3-二氯苯基）-3,5-吡啶二甲酸甲乙酯（1）,2,6-二甲基-4-（2,3-二氯苯基）-1,4-二氢-3,5-吡啶二甲酸二甲酯（2）和2,6-二甲基-4-（2,3-二氯苯基）-1,4-二氢-3,5-吡啶二甲酸二乙酯（3）,其结构经1H NMR和MS确证.1～3的合成,为非洛地平生产、检验、贮存过程中对杂质的控制提供了依据.

Impurity in bulk drugs Felodipin recorded in EP7.8,3,5-pyridinedicarboxylic acid-4-（2,3-dichlorophenyl）-2,6-dimethyl-3-ethyl-5-methyl ester （1）,3,5-pyridinedicarboxylic acid-4-（2,3-dichlorophenyl）-1,4-dihydro-2,6-dimethyl-3,5-dimethyl ester （2） and 3,5-pyridinedicarboxylic acid4-（2,3-dichlorophenyl）-1,4-dihydro-2,6-dimethyl-3,5-diethyl ester （3） were synthesized.The structures were confirmed by 1H NMR and MS.Synthesis of 1 ～ 3 provide the basis for control of the impurity in the process of production,inspection and storage.