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10-羟基喜树碱首先在N,N-二甲基甲酰胺(DMF)中经N-溴代丁二酰亚胺(NBS)溴代得到9-溴-10-羟基喜树碱,9-溴-10-羟基喜树碱和氯甲酸乙酯反应得到9-溴-10-羟基喜树碱-10,20-双乙氧基碳酸酯(6).化合物6和烯丙基三正丁基锡通过Stille偶联反应[9]得到关键中间体7,最后水解化合物7得到目标化合物.通过柱层析纯化得到纯度大于99.8%,单杂小于0.1%的吉咪替康(HPLC).所有中间体及目标产物经1HNMR,13CNMR,LRMS,HRMS表征确证.
Hydroxycamptothecin is first brominated with N-bromosuccinimide (NBS) in N, N-dimethylformamide (DMF) to give 9-bromo-10-hydroxycamptothecin, Reaction of bromo-10-hydroxycamptothecin with ethyl chloroformate gave 9-bromo-10-hydroxycamptothecin-10,20-bisethoxycarbonate (6) Compound 6 and allyltri- Stille coupling reaction [9] gave the key intermediate 7 and finally hydrolyzed compound 7 to give the title compound, which was purified by column chromatography to obtain gemcitabine (HPLC) with purity more than 99.8% and single impurity less than 0.1% .All the intermediates and The target product was confirmed by 1HNMR, 13CNMR, LRMS and HRMS.