4-溴-N-(2-(2,6-二氧哌啶-3-基)-1,3-二氧异吲哚-4-基)丁酰胺的合成

Synthesis of 4-Bromo-N-(2-(2,6-dioxypiperidine-3-yl)-1,3-dioxyisole-4-yl) butamide

以3-氨基-N-(2,6-二氧代-3-哌啶基)邻苯二甲酰亚胺(泊马度胺,化合物1)和4-溴丁酰氯(化合物2)为原料,经过取代反应得到目标产物4-溴-N-(2-(2,6-二氧哌啶-3-基)-1,3-二氧异吲哚-4-基)丁酰胺,其结构经过^(1)H NMR、^(13)C NMR、MS进行确证,并进一步对产物收率的影响因素进行了考察,确定最佳反应条件为:在氮气保护下,物料比n(化合物1)∶n(化合物2)=1∶3,反应溶剂为无水四氢呋喃(加入有机碱三乙胺),回流反应时间为4 h。在此条件下,目标产物收率为54.5%。

Taking 3-amino-N-(2,6-dioxyd-3-piperidyl) phthalates (compound 1) and 4-bromine butyl chloride(compound 2) as raw materials,the target product 4-bromo-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)butanamide was obtained via substitution reaction,the structure of the target compound was confirmed by ^(1)H NMR,^(13)C NMR and MS.Further investigation was made on the factors affecting the yield of the product,and the optimum reaction conditions were determined as follow:under the protection of nitrogen,n (compound 1)∶n (compound 2)=1∶3,using 99.5%tetrahydrofuran as solvent (adding triethylamine),the reaction time 4 h.Under these conditions,the yield of the target compound was 54.5%.