目的研究检查点激酶Bub1抑制剂2OH-BNPP1的合成方法。方法将2-羟基苯乙酸转化成苄基保护的酰氯,再与丙二腈缩合得化合物5,经硫酸二甲酯对5的烯醇式甲基化得化合物6,6与叔丁基肼反应完成了吡唑环的构筑以形成化合物7,7与甲酰胺作用构筑并嘧啶环,最后将所得的化合物8脱苄,即得目标物2OH-BNPP1(1)。结果与结论以苄基保护起始原料的2-位酚羟基,使路线中的各步中间体稳定、极性小而易于硅胶柱色谱分离,最后催化脱苄几乎定量完成,保证了终产物的化学纯度。目标物经HPLC检测纯度为98.8%,其结构经ESI-MS和1H-NMR确证。 Objective To study the synthesis of checkpoint kinase Bub1 inhibitor 2OH-BNPP1. Methods 2-Hydroxyphenylacetic acid was transformed into benzyl protected acyl chloride, which was then condensed with malononitrile to give compound 5. Enolate methylation of 5 with dimethyl sulfate afforded compound 6,6 and tert-butyl hydrazine The pyrazole ring is completed to form a compound 7,7 and the pyrimidine ring is formed by the action of formamide. Finally, the resulting compound 8 is debenzylated to obtain the target 2OH-BNPP1 (1). RESULTS AND CONCLUSION The phenolic hydroxyl group at the 2-position of the starting material was protected with benzyl to make the intermediate in each step of the route stable, of small polarity and easy to separate by silica gel column chromatography. Finally, the amount of benzylalcohol was almost quantitatively determined, Chemical purity. The purity of the target was 98.8% by HPLC. Its structure was confirmed by ESI-MS and 1H-NMR.