反应详情

温度

100 °C

DIPEA (0.408 mL, 2.33 mmol) was added to a mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine. 0.8 toluene-4-sulfonic acid salt (Intermediate 87, 330 mg, 0.58 mmol) in DMA (3 mL). N,N-Dimethylazetidin-3-amine dihydrochloride (Intermediate 26, 121 mg, 0.70 mmol) was then added in one portion. The mixture was heated in a microwave at 100° C. for 0.5 h then the mixture was cooled and diluted with CH3OH and absorbed onto an SCX column. The column was washed with CH3OH and eluted with 1:1 methanolic ammonia in CH2Cl2. Appropriate fractions were concentrated in vacuo. Further purification by FCC, eluting with 1-10% CH3OH in CH2Cl2 gave the title compound (295 mg, 100%) as a brown gum; 1H NMR: (CDCl3) 2.18 (6H, s), 3.13-3.24 (1H, m), 3.67-3.75 (2H, m), 3.89 (3H, s), 3.96 (3H, s), 4.13 (2H, t), 6.04 (1H, s), 7.21-7.29 (1H, m, partially obscured by chloroform signal), 7.29-7.41 (3H, m), 8.22 (1H, s), 8.37 (1H, s), 8.46 (1H, d), 9.05 (1H, s); m/z: ES+ MH+ 508.

1. temperaturethe mixture was cooled
2. customabsorbed onto an SCX column
3. washThe column was washed with CH3OH
4. washeluted with 1:1 methanolic ammonia in CH2Cl2
5. concentrationAppropriate fractions were concentrated in vacuo
6. customFurther purification by FCC
7. washeluting with 1-10% CH3OH in CH2Cl2