【摘要】 2-甲氧基-4-氨基苯甲酸甲酯(4)与米氏酸缩合后,经环合、氯代及氨解制得4-氯-7-甲氧基喹啉-6-甲酰胺(8)。另以邻氯硝基苯(9)经还原转位、酰化、成脲制得1-(2-氯-4羟基苯基)-3-环丙基脲(12)。8与12经亲核取代制得抗肿瘤药lenvatinib,总收率约39%(以4计),纯度99.8%。更多还原

【Abstract】 4-Chloro-7-methoxyquinoline-6-carboxamide(8) was synthesized from methyl 4-amino-2-methoxybenzoate(4) by condensation with Meldrum’s acid, ring closure, chlorination and aminolysis. While the intermediate 1-(2-chloro-4-hydroxyphenyl)-3-cyclopropylurea(12) can be obtained from ο-nitrochlorobenzene by reduction, translocation, acylation and substitution. Lenvatinib, an antitumor agent, was synthesized from 8 and 12 by nucleophilic substitution with an overall yield of about 39%(based on compound 4) and an HPLC purity of 99.8%.更多还原