反应详情

To a solution of 4-(trifluoromethyl)-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 27) (241 mg, 0.51 mmol) in 1,2-dichloroethane (20 mL) was added phosphorus oxychloride (0.37 mL, 4.0 mmol). The mixture was heated to reflux for 24 hours. After cooling to room temperature, the mixture was diluted with DCM and aqueous (saturated) Na2CO3. The aqueous was extracted with DCM and the combined organic layers were washed with brine, dried over Na2SO4, concentrated under vacuum and purified by silica gel chromatography to give 5-methyl-7-[4-(trifluoromethyl)phenyl]-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (0.007 g) as yellow solid. 1H NMR (CDCl3): δ8.85 (s, 1H), 8.86 (d J=8.24 Hz, 2H), 7.72 (d, J=8.24 Hz, 2H), 6.88 (m, 3H), 3.87 (s, 3H), 3.83 (s, 6H), 2.63 (s, 3H). MS m/z 459 (M+1).

1. temperatureThe mixture was heated
2. temperatureto reflux for 24 hours
3. extractionThe aqueous was extracted with DCM
4. washthe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated under vacuum
7. custompurified by silica gel chromatography