反应详情

温度

25 °C

A dry nitrogen-flushed 5 L 4-neck round bottom flask is charged with 100 g (Purity: 98%, 0.389 mol 1.0 eq.) of 3-(2-chloro-4-(cyclopentylamino)pyrimidin-5-yl)prop-2-yn-1-ol, (A1d), 880 g (1000 mL) of peroxide free tetrahydrofuran and 753 g, (856 mL) of tetrabutylammonium fluoride, 1.0M solution in THF. The content is stirred at 25° C. for 10 min, and then the solution is warmed to 60° C. This temperature is maintained for 1.5 h until the starting material, A1d, is ≦2.5±0.5% as determined by HPLC analysis. The resulting solution is cooled to below 30±3° C.2, and distilled under reduced pressure to remove THF. 79 g (100 mL) of 2-propanol is added. The sample is stirred for 15 min and 1000 g (1000 mL) of water then add slowly over 30 min The sample is stirred at 20±3° C. for 30 min and then filtered. The cake is washed twice with 200 g (2×100 mL) of water. The solids are dried at 50° C. for 16 h to afford Compound A1c as a tan, crystalline solid, mp=174-176° C.

1. customA dry nitrogen-flushed 5 L 4-neck round bottom flask
2. temperaturethe solution is warmed to 60° C
3. temperatureThis temperature is maintained for 1.5 h until the starting material
4. temperatureThe resulting solution is cooled to below 30±3° C
5. distillation2, and distilled under reduced pressure
6. customto remove THF
7. addition79 g (100 mL) of 2-propanol is added
8. stirringThe sample is stirred for 15 min
9. addition1000 g (1000 mL) of water then add slowly over 30 min The sample
10. stirringis stirred at 20±3° C. for 30 min
11. filtrationfiltered
12. washThe cake is washed twice with 200 g (2×100 mL) of water
13. customThe solids are dried at 50° C. for 16 h
14. customto afford Compound A1c as a tan, crystalline solid, mp=174-176° C.