反应详情

温度

65 °C

To a solution of 1.45 g of 3-(1-methylpiperidin-4-yl)propan-1-ol in 40 ml of tetrahydrofuran are added 360 mg of sodium hydride. The white suspension formed is stirred for 15 minutes at 65° C., cooled and mixed with 1.45 g of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline, whereupon the mixture suddenly turns dark red. The reaction mixture is stirred first for 10 minutes at ambient temperature, then for 45 minutes at 65° C. As the reaction is not yet complete, a further 150 mg of sodium hydride are added and the mixture is stirred for a further 45 minutes at 65° C. The solvent is distilled off using a rotary evaporator and the brown residue is stirred with 50 ml of ice water. The aqueous phase is extracted with methylene chloride. The combined extracts are washed with water, dried over sodium sulfate and concentrated by evaporation. The crude product is purified by chromatography over a silica gel column with methylene chloride/methanol/concentrated ammonia solution (90:10:0.05). Yield: 1.30 g of (65% of theory); Rf value: 0.28 (silica gel, methylene chloride/methanol/concentrated aqueous ammonia solution=90:10:0.1); mass spectrum (ESI+): m/z=500, 502 [M+H]+.

1. customThe white suspension formed
2. temperaturecooled
3. stirringThe reaction mixture is stirred first for 10 minutes at ambient temperature
4. waitfor 45 minutes at 65° C
5. stirringthe mixture is stirred for a further 45 minutes at 65° C
6. distillationThe solvent is distilled off
7. customa rotary evaporator
8. stirringthe brown residue is stirred with 50 ml of ice water
9. extractionThe aqueous phase is extracted with methylene chloride
10. washThe combined extracts are washed with water
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated by evaporation
13. customThe crude product is purified by chromatography over a silica gel column with methylene chloride/methanol/concentrated ammonia solution (90:10:0.05)