反应详情

温度

100 °C

To a suspension of 3-bromo-8-(2,4-difluorophenyl)-1-methylpyrido[3,2-d]pyridazin-2(1H)-one (8) (80.0 mg, 0.227 mmol) in 3:1 1,4-dioxane: 1 M aq Na2CO3 (3.2 mL) was added N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (82.1 mg, 0.273 mmol) and tetrakis(triphenylphosphine)palladium (0) (21.0 mg, 0.0182 mmol). The reaction mixture was stirred and heated in a microwave at 100° C. for 55 min and then cooled to room temperature. The mixture was diluted with water and extracted with CHCl3/iPrOH (4:1). The combined organic extract was washed with 2 M Na2CO3, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography [eluting with a gradient of 40-50% B in A where the eluents were: A=CH2Cl2; B=4% MeOH in EtOAc] to give N-cyclopropyl-3-(8-(2,4-difluorophenyl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyridazin-3-yl)-4-methylbenzamide as a white solid. MS (ESI, pos. ion) m/z: 447 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.52-0.60 (m, 2H), 0.64-0.73 (m, 2H), 2.21 (s, 3H), 2.85 (td, J=3.9, 7.3 Hz, 1H), 3.16 (s, 3H), 7.32-7.42 (m, 2H), 7.45-7.54 (m, 1H), 7.74 (d, J=1.4 Hz, 1H), 7.79-7.91 (m, 2H), 8.19 (s, 1H), 8.41 (d, J=3.9 Hz, 1H), 9.45 (s, 1H).

1. temperaturecooled to room temperature
2. extractionextracted with CHCl3/iPrOH (4:1)
3. extractionThe combined organic extract
4. washwas washed with 2 M Na2CO3
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel chromatography [
9. washeluting with a gradient of 40-50% B in A where the eluents