Ethyl Acetate → HCID 135936828, compound

Temperature

60 °C

A mixture of N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (8.00 g, 13.8 mmol), 1,4-dioxane (80 mL) and 1 N aqueous NaOH (30.0 mL, 30.0 mmol) was heated at about 60° C. for about 2 h. Then the reaction was diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude mixture was purified by silica gel chromatography eluting with a gradient of 0-100% DCM/MeOH/Et2NH (970:27:3) in DCM followed by DCM/MeOH/Et2NH (950:45:5). The product-containing fractions were combined, concentrated under reduced pressure, and dried in a vacuum oven at about 70° C. for about 12 h to give a solid. The solid was triturated with Et2O, filtered while washing with additional Et2O, and dissolved in hot MeOH. The solution was concentrated under reduced pressure to give a solid. The solid was dissolved in hot MeOH (200 mL), sonicated while cooling until a suspension formed, concentrated under reduced pressure, and dried in a vacuum oven at about 50° C. to give an off-white solid. To the solid was added EtOAc (30 mL) to give a suspension which was heated briefly with a heat gun and then sonicated for about 15 min. After sitting at ambient temperature for about 15 min, the resulting white solid was collected by vacuum filtration, washing with additional EtOAc (15 mL), and dried in a vacuum oven at about 50° C. The solid was dissolved in hot EtOH (˜200 mL), filtered to remove minor insolubles (<10 mg), sonicated for about 10 min, while cooling, to give a white suspension, which was concentrated under reduced pressure. The resulting white solid was dried in a vacuum oven at about 60° C. to give N-((1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (3.43 g, 67%): LC/MS (Table 2, Method a) Rt=1.67 min; MS m/z: 375 (M+H)+.

1. extractionextracted with EtOAc (3×100 mL)
2. washThe combined organic layers were washed with brine (100 mL)
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude mixture was purified by silica gel chromatography
7. washeluting with a gradient of 0-100% DCM/MeOH/Et2NH (970:27:3) in DCM
8. concentrationconcentrated under reduced pressure
9. customdried in a vacuum oven at about 70° C. for about 12 h
10. customto give a solid
11. customThe solid was triturated with Et2O
12. filtrationfiltered
13. washwhile washing with additional Et2O
14. dissolutiondissolved in hot MeOH
15. concentrationThe solution was concentrated under reduced pressure
16. customto give a solid
17. customsonicated
18. temperaturewhile cooling until a suspension
19. customformed
20. concentrationconcentrated under reduced pressure
21. customdried in a vacuum oven at about 50° C.
22. customto give an off-white solid
23. customto give a suspension which
24. temperaturewas heated briefly with a heat gun
25. customsonicated for about 15 min
26. filtrationthe resulting white solid was collected by vacuum filtration
27. washwashing with additional EtOAc (15 mL)
28. customdried in a vacuum oven at about 50° C
29. dissolutionThe solid was dissolved in hot EtOH (˜200 mL)
30. filtrationfiltered
31. customto remove minor insolubles (<10 mg)
32. customsonicated for about 10 min
33. temperaturewhile cooling
34. customto give a white suspension, which
35. concentrationwas concentrated under reduced pressure
36. customThe resulting white solid was dried in a vacuum oven at about 60° C.

ORD record

ord-e16803c0bed94a38b764051094325362

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962629B2