反应详情

温度

140 °C

A mixture of 5-methyl-2,5-diazaspiro[3.4]octane dihydrochloride salt (Intermediate 47, 400 mg) in CH3OH/water was absorbed onto an SCX column. The column was washed with CH3OH and eluted with methanolic ammonia. The fractions containing product were combined and concentrated (caution: product is volatile). A mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 20, 250 mg, 0.60 mmol), 5-methyl-2,5-diazaspiro[3.4]octane (91 mg, 0.72 mmol) and DIPEA (0.365 mL, 2.11 mmol) in DMA (3 mL) was heated at 140° C. for 0.5 h in a microwave. The mixture was then diluted with CH3OH and absorbed onto an SCX column. The column was washed with CH3OH and eluted with 1:1 methanolic ammonia in CH2Cl2. Fractions containing the product were combined and concentrated to provide a solid. This solid was suspended in CH3OH, filtered, washed with diethyl ether and dried to give the title compound (267 mg, 85%) as a red solid; 1H NMR: 1.63-1.78 (2H, m), 2-2.12 (2H, m), 2.41 (3H, s), 2.69 (2H, t), 3.77 (2H, d), 3.90 (3H, s), 4.13 (2H, d), 6.30 (1H, s), 7.14 (1H, td), 7.34 (1H, t), 8.12 (1H, s), 8.41-8.46 (2H, m), 8.74 (1H, s), 8.86 (1H, d), 8.96 (1H, s); m/z: ES+ MH+ 521.46.

1. customwas absorbed onto an SCX column
2. washThe column was washed with CH3OH
3. washeluted with methanolic ammonia
4. additionThe fractions containing product
5. concentrationconcentrated (caution: product is volatile)
6. customabsorbed onto an SCX column
7. washThe column was washed with CH3OH
8. washeluted with 1:1 methanolic ammonia in CH2Cl2
9. additionFractions containing the product
10. concentrationconcentrated
11. customto provide a solid
12. filtrationfiltered
13. washwashed with diethyl ether
14. customdried