论文部分内容阅读
目的优化抗帕金森病药伊曲茶碱1的合成工艺以适用于工业化生产。方法将碳酸二甲酯和乙胺经缩合、环合、亚硝化、还原得1,3-二乙基-5,6-二氨基尿嘧啶(6),化合物6与(E)-3,4-二甲氧基苯丙烯酸(8)进行缩合、闭环、甲基化反应制得伊曲茶碱1。化合物8可由3,4-二甲氧基苯甲醛(7)和丙二酸经Knoevenagel缩合反应制得。中间体及目标化合物经过MS和~1H-NMR确证。结果与结论对各关键工艺质量控制点的工艺进行优化,使合成总收率达26.2%,产品纯度为99.76%。改进后的工艺条件温和,操作简便,无需柱层析,适合工业化生产。
OBJECTIVE To optimize the synthetic process of anti-Parkinson’s disease imattoplline 1 for industrial production. Methods Dimethyl carbonate and ethylamine were condensed, cyclized and nitrosated to give 1,3-diethyl-5,6-diaminouracil (6). Compound 6 and (E) - dimethoxybenzene acrylic acid (8) for condensation, ring closure, methylation reaction imatophyll 1. Compound 8 can 3,4-dimethoxybenzaldehyde (7) and malonic acid by Knoevenagel condensation reaction. The intermediates and target compounds were confirmed by MS and ~ 1H-NMR. Results and Conclusion The process of each key process quality control point was optimized so that the total synthesis yield reached 26.2% and the product purity was 99.76%. The improved process conditions are mild, easy to operate, without column chromatography, suitable for industrial production.