反应详情

温度

97 °C

1500 ml of phosphorus oxychloride and 300 g of 4-(4-Amino-6-hydroxypyrimidin-2-ylamino)benzonitrile at 27±3° C. were added to the reaction vessel and heated to 97±3° C.; and maintained at same temperature for 7 hrs. After completion of the reaction, ˜50% of phosphorous oxychloride was distilled off under vacuum at 83±2° C. and the reaction mixture was cooled to 30±5° C. In a clean RB flask were added 1000 g of ice and 1000 mL of water and such was slowly added the above obtained reaction mass. The pH of the reaction mass was adjusted to 9.0±0.5 with 50% potassium carbonate solution in water at 5±5° C. The reaction mixture was stirred, filtered and the obtained solid was washed with 600 ml of water and suck dried. The wet solid was charged into a RB flask at 27±3° C. to which was added 600 ml of water. The resulting wet solid was taken into a RB flask and 600 ml of water was added, stirred, and filtered. The obtained solid was washed with water and suck dried. 3000 ml of ethyl acetate was charged into a RB flask and to this was added the obtained solid and heated to 43±3° C. The reaction mass was stirred for 20 mins and filtered hot. The residue was washed with ethyl acetate and filtrate (1) collected at 27±3° C. The obtained solid was again taken in RB flask to which was added 1500 ml of ethyl acetate and heated to 43±3° C., stirred and the hot reaction mass filtered and the filtrate (2) collected. Both filtrates (1) and (2) were taken and distilled off solvent at 47±3° C. To the residue was added 900 ml of heptane and cooled to 27±3° C. and was again added 1100 ml of heptane, stirred, the solid filtered and suck dried, and the solid was washed with heptane. The obtained solid was dried under vacuum. To the obtained 190 g of crude was added 380 ml of dimethyl formamide and 20.4 ml of 1,8-diazabicycloundec-7-ene under stirring at 27±3° C. and the reaction mass heated to 47±3° C. To the obtained clear solution was added 760 ml of water and stirred for 1 hr. The reaction mass was cooled and filtered. The solid was washed with 760 mL of water twice and suck dried. The solid was washed with 48 ml of chilled methanol and the solid suck dried. The obtained solid was further dried under vacuum to yield the title compound.

1. temperatureand maintained at same temperature for 7 hrs
2. distillationwas distilled off under vacuum at 83±2° C.
3. temperaturethe reaction mixture was cooled to 30±5° C
4. additionIn a clean RB flask were added 1000 g of ice and 1000 mL of water and such
5. additionwas slowly added the
6. customabove obtained
7. customreaction mass
8. filtrationfiltered
9. washthe obtained solid was washed with 600 ml of water and suck
10. customdried
11. additionThe wet solid was charged into a RB flask at 27±3° C. to which
12. additionwas added 600 ml of water
13. additionwas added
14. stirringstirred
15. filtrationfiltered
16. washThe obtained solid was washed with water and suck
17. customdried
18. addition3000 ml of ethyl acetate was charged into a RB flask
19. additionto this was added the obtained solid
20. temperatureheated to 43±3° C
21. stirringThe reaction mass was stirred for 20 mins
22. filtrationfiltered hot
23. washThe residue was washed with ethyl acetate and filtrate (1)
24. customcollected at 27±3° C
25. additionwas added 1500 ml of ethyl acetate
26. temperatureheated to 43±3° C.
27. stirringstirred
28. filtrationthe hot reaction mass filtered
29. customthe filtrate (2) collected
30. distillationdistilled off solvent at 47±3° C
31. additionTo the residue was added 900 ml of heptane
32. temperaturecooled to 27±3° C.
33. stirringstirred
34. filtrationthe solid filtered
35. customsuck dried
36. washthe solid was washed with heptane
37. customThe obtained solid was dried under vacuum
38. additionTo the obtained 190 g of crude was added 380 ml of dimethyl formamide and 20.4 ml of 1,8-diazabicycloundec-7-ene
39. stirringunder stirring at 27±3° C.
40. temperaturethe reaction mass heated to 47±3° C
41. additionTo the obtained clear solution was added 760 ml of water
42. stirringstirred for 1 hr
43. temperatureThe reaction mass was cooled
44. filtrationfiltered
45. washThe solid was washed with 760 mL of water twice
46. customsuck dried
47. washThe solid was washed with 48 ml of chilled methanol
48. customthe solid suck dried
49. customThe obtained solid was further dried under vacuum