تفاعل #610480
ord-a96a1da716154721862c1550ba14c626
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 DCM and MeOH
- 5أخرىdried
- 6تركيزconcentrated
- 7أخرىThe residue was purified by column chromatography on silica gel
- 8غسيلeluting with EtOAc-hexanes
الإجراء التجريبي
A mixture of 4-bromo-3-chloro-7-(2-hydroxypropan-2-yl)-9H -carbazole-1-carboxamide [Intermediate 3] (0.051 g, 0.135 mmol), 5-methoxy-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 32] (0.050 g, 0.122 mmol) and Cs2CO3 (0.080 g, 0.245 mmol) in THF (2 mL) and water (0.5 mL) was bubbled with nitrogen for 2 min, then was treated with PdCl2(dppf) DCM adduct (5.0 mg, 6.12 μmol). 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 DCM and MeOH, dried and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc-hexanes, to give 3-chloro-7-(2-hydroxypropan-2-yl)-4-(3-(5-methoxy-1,3-dioxo-1H-pyrido[1,2-c]pyrimidin-2(3H)-yl)-2-methylphenyl)-9H-carbazole-1-carboxamide (mixture of four atropisomers) as a yellow solid (32.8 mg, 44% yield). Mass spectrum m/z 583 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.51-11.47 (m, 1H), 8.27 (br. s., 1H), 8.14 (d, J=1.5 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H), 7.83 (s, 1H), 7.59 (br. s., 1H), 7.55-7.45 (m, 3H), 7.30-7.25 (m, 1H), 7.03-6.97 (m, 1H), 6.71 (d, J=8.1 Hz, 1H), 6.56 (q, J=7.6 Hz, 1H), 5.90 (s, 1H), 4.98 (s, 1H), 3.91 (s, 3H), 1.69 (s, 3H), 1.45-1.42 (m, 6H).