反应详情

温度

45 °C

A mixture of (2R)—N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide (783 mg, 3 mmol), triphenylphosphine (2.35 g, 9 mmol) and carbon tetrachloride (8.62 ml, 90 mmol) in 1,2-dichloroethane (20 ml) was stirred at 45° C. for 2 hours. The mixture was cooled and the solvents were evaporated under vacuum. 1-(Pyridin-2-ylmethyl)-1H-indazol-5-amine (706 mg, 3.15 mmol) and acetonitrile (15 ml) were added. The mixture was stirred at 75° C. for 1 hour. After cooling, the solvents were evaporated under vacuum. The residue was diluted in DCM and extracted with 2N hydrochloric acid. The aqueous layer was neutralised by addition of 6N aqueous ammonia and extracted with DCM. The DCM layer was dried over magnesium sulfate and the solvents were evaporated under vacuum. The residue was purified twice by chromatography on silica gel (first eluant: 3% 6N methanolic ammonia in DCM; second eluant: 3% methanol in DCM) to give the title compound as a white foam (600 mg, 43%); NMR Spectrum (CDCl3) 1.72 (d, 3H), 3.06 (s, 3H), 3.14 (s, 3H), 5.43 (q, 1H), 5.75 (s, 2H), 6.81 (m, 2H), 7.17 (m, 1H), 7.41 (d, 1H), 7.48 (d, 1H), 7.62-7.53 (m, 2H), 7.81 (dd, 1H), 8.10 (s, 1H), 8.44 (d, 1H), 8.58 (d, 1H), 8.62 (s, 1H); Mass spectrum 468.

1. temperatureThe mixture was cooled
2. customthe solvents were evaporated under vacuum
3. stirringThe mixture was stirred at 75° C. for 1 hour
4. temperatureAfter cooling
5. customthe solvents were evaporated under vacuum
6. additionThe residue was diluted in DCM
7. extractionextracted with 2N hydrochloric acid
8. additionThe aqueous layer was neutralised by addition of 6N aqueous ammonia
9. extractionextracted with DCM
10. dry with materialThe DCM layer was dried over magnesium sulfate
11. customthe solvents were evaporated under vacuum
12. customThe residue was purified twice by chromatography on silica gel (first eluant: 3% 6N methanolic ammonia in DCM; second eluant: 3% methanol in DCM)