反应详情

1-(2-Formyl-3-iodophenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile (71 mg, 0.135 mmol), 6-tert-butylphthalazin-1(2H)-one (27.2 mg, 0.135 mmol), cuprous iodide (25.6 mg, 0.135 mmol) and sodium bicarbonate (22.6 mg, 0.269 mmol) were combined in 2 mL of DMSO. The mixture was thoroughly degassed with argon and then stirred in an oil bath preheated to 100° C. After 1 hr, the mixture was extracted with dichloromethane and water. The organic layer was dried over sodium sulfate and filtered. Solvents were evaporated and the residue was purified by flash column chromatography (12 g silica gel, 0% to 5% methanol in dichloromethane) to give 1-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-3-[4-(morpholine-4-carbonyl)phenylamino]-1H-pyrazole-4-carbonitrile as a pale pink solid (34 mg, 42% yield). LC/MS clacd for C34H31N7O4 (m/e) 601.24, obsd 602.1 (M+H, ES+); 1H NMR (400 MHz, CDCl3) δ ppm 1.45 (s, 9H), 3.68 (br. m., 8H), 6.68 (br. s., 1H), 7.39 (d, J=8.6 Hz, 2H), 7.46 (d, J=8.6 Hz, 2H), 7.57 (dd, J=8.0, 1.1 Hz, 1H), 7.65-7.74 (m, 1H), 7.74-7.81 (m, 2H), 7.93 (dd, J=8.6, 1.8 Hz, 1H), 8.17 (s, 1H), 8.40 (d, J=8.6 Hz, 1H), 8.47 (br. s., 1H), 9.90 (br. s., 1H).

1. customThe mixture was thoroughly degassed with argon
2. custompreheated to 100° C
3. extractionthe mixture was extracted with dichloromethane and water
4. dry with materialThe organic layer was dried over sodium sulfate
5. filtrationfiltered
6. customSolvents were evaporated
7. customthe residue was purified by flash column chromatography (12 g silica gel, 0% to 5% methanol in dichloromethane)