反应详情

温度

40 °C

To a solution of the above 5-cycloheptyl-6-(2,4,6-trifluorophenyl)imidazo[1,2-a]pyrimidin-7-ol and 3-dimethylamino-1-propanol (206 m g, 2.0 mmol) in 3.0 mL of dimethylsulfoxide at room temperature is added sodium hydride (60% in mineral oil, 80 mg, 2.0 mmol). The mixture is heated at 40° C. for 2 h, and cooled to room temperature. A saturated sodium chloride solution is added, and the product is extracted with ethyl acetate. The organic solution is washed with saturated sodium chloride (×3), dried over magnesium sulfate, and concentrated. To the residue is added 5 mL of phosphorous oxychloride and 2 mL of N,N-diethylaniline, and the mixture is heated at 110° C. for 1 h. The excess phosphorous oxychloride is removed in vaccuo, and the resulting residue is partitioned between ethyl acetate and 5% sodium carbonate solution. The organic layer is washed with saturated sodium chloride, dried over magnesium sulfate, and concentrated. The residue is chromatographed over silica gel, eluting with a gradient of ethyl acetate to 20% methyl alcohol in ethyl acetate. Concentration provides 3-[4-(7-chloro-5-cycloheptylimidazo[1,2-a]pyrimidin-6-yl)-3,5-difluorophenoxy]-N,N-dimethylpropan-1-amine as a brown oil (24 mg). MS: m/z 463.3 (M+H).

1. temperaturecooled to room temperature
2. extractionthe product is extracted with ethyl acetate
3. washThe organic solution is washed with saturated sodium chloride (×3)
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated
6. additionTo the residue is added 5 mL of phosphorous oxychloride and 2 mL of N,N-diethylaniline
7. temperaturethe mixture is heated at 110° C. for 1 h
8. customThe excess phosphorous oxychloride is removed in vaccuo
9. customthe resulting residue is partitioned between ethyl acetate and 5% sodium carbonate solution
10. washThe organic layer is washed with saturated sodium chloride
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated
13. customThe residue is chromatographed over silica gel
14. washeluting with a gradient of ethyl acetate to 20% methyl alcohol in ethyl acetate
15. concentrationConcentration