反应详情

温度

0 °C

To a solution of 7-amino-5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one (150 mg, 0.278 mmol) (COMPOUND CCC4, STEP A) in 4 mL of THF cooled to 0° C. was added 1-methyl-1H-imidazole-4-sulfonyl chloride (100 mg, 0.556 mmol). A few crystals of 4-(dimethylamino)pyridine and diisopropylethylamine (53.9 mg, 0.417 mmol) were added. The resulting reaction mixture was stirred at 0° C. for 20 min, then heated to 70° C. for ca. 7.5 h. The reaction mixture was cooled to rt and partitioned between ethyl acetate and 1M aqueous HCl (added brine to improve the layer separation). The organic layer was concentrated under reduced pressure and triturated sequentially with Et2O, methanol, and CH2Cl2 to yield the N-[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]-1-methyl-1H-imidazole-4-sulfonamide. Mass spectrum (ESI) 682.0 (M+1).

1. customThe resulting reaction mixture
2. temperatureheated to 70° C. for ca. 7.5 h
3. temperatureThe reaction mixture was cooled to rt
4. custompartitioned between ethyl acetate and 1M aqueous HCl (
5. additionadded brine
6. customthe layer separation)
7. concentrationThe organic layer was concentrated under reduced pressure
8. customtriturated sequentially with Et2O, methanol, and CH2Cl2