تفاعل #610482
ord-3566380873e54ffa81e1a3f3335f55de
معادلة التفاعل
المتفاعلات
الكواشف
ظروف التفاعل
المعالجة
- 1أخرىwas bubbled with nitrogen for 2 min
- 2أخرىBubbling with nitrogen
- 3أخرىthe reaction vessel was sealed
- 4workup.ADDITIONThe cooled mixture was diluted with EtOAc
- 5غسيلwashed sequentially with water and brine
- 6استخلاصThe combined aqueous layers were extracted with DCM
- 7أخرىwere dried
- 8تركيزconcentrated
- 9أخرىThe residue was purified by column chromatography on silica gel
- 10غسيلeluting with EtOAc-hexanes
الإجراء التجريبي
A mixture of 4-bromo-3-fluoro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide [Intermediate 27] (0.200 g, 0.548 mmol), 5-fluoro-2-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrido[1,2-c]pyrimidine-1,3(2H)-dione [Intermediate 37] (0.260 g, 0.657 mmol) and Cs2CO3 (0.357 g, 1.10 mmol) in dioxane (4 mL) and water (1 mL) was bubbled with nitrogen for 2 min, then was treated with PdCl2(dppf) DCM adduct (0.022 g, 0.027 mmol). Bubbling with nitrogen was continued for 30 sec and the reaction vessel was sealed. The mixture was heated at 60° C. overnight. The cooled mixture was diluted with EtOAc and washed sequentially with water and brine. The combined aqueous layers were extracted with DCM, and combined organic layers were dried and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc-hexanes, to give 3-fluoro-4-(3-(5-fluoro-1,3-dioxo-1H-pyrido[1,2-c]pyrimidin-2(3H)-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (mixture of four atropisomers) as a yellow solid (0.194 g, 63% yield).