反应详情

温度

75 °C

4N Hydrogen chloride in dioxane (9.6 ml, 38.4 mmol) was added to a mixture of 1-(pyridin-2-ylmethyl)-1H-indazol-5-amine (8.78 g, 39.2 mmol) and 4-chloro-5-fluoroquinazoline (7 g, 38.4 mmol; prepared as described in WO 2001/094341) in acetonitrile (100 ml). The mixture was stirred at 75° C. for 1.5 hours. After cooling, the mixture was evaporated to dryness. The residue was diluted in 6N methanolic ammonia. The mixture was evaporated to dryness and was diluted in DCM. After filtration of the solids, the filtrate was evaporated to dryness. The residue was purified by chromatography on silica gel (eluant: methanol in DCM) to give 5-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine as a beige solid (10.2 g, 72%); NMR spectrum (CDCl3) 5.76 (s, 2H), 6.89 (d, 1H), 7.22-7.18 (m, 2H), 7.58-7.45 (m, 3H), 7.72 (m, 2H), 8.11 (s, 1H), 8.21 (s, 1H), 8.47 (m, 1H), 8.60 (d, 1H), 8.68 (s, 1H); Mass spectrum MH+ 371.

1. temperatureAfter cooling
2. customthe mixture was evaporated to dryness
3. additionThe residue was diluted in 6N methanolic ammonia
4. customThe mixture was evaporated to dryness
5. additionwas diluted in DCM
6. filtrationAfter filtration of the solids
7. customthe filtrate was evaporated to dryness
8. customThe residue was purified by chromatography on silica gel (eluant: methanol in DCM)