Cyclopropanesulfonyl chloride → N-((1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide

To a mixture of (1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine hydrochloride (0.300 g, 0.952 mmol) in DMF (9 mL) was added TEA (0.462 mL, 3.33 mmol) and cyclopropanesulfonyl chloride (0.097 mL, 0.95 mmol). After about 1.5 h at ambient temperature, the reaction was diluted with water (10 mL) and extracted with DCM (3×15 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. To the crude material was added MeOH (˜50 mL) and a small amount of insoluble material (<0.01 g) was filtered. Silica gel (2 g) was added to the filtrate and the mixture was concentrated under reduced pressure. The silica mixture was purified by silica gel chromatography eluting with a step-wise gradient of DCM/MeOH/NH4OH 990:9:1 to 980:18:2 to give an off-white solid that was dried in a vacuum oven at about 70° C. The solid was dissolved in hot MeOH. The resulting material was filtered while hot to remove particulates. The filtrate was sonicated while cooling to get a fine suspension which was then concentrated under reduced pressure and dried in a vacuum oven at about 100° C. to give N-((1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (0.21 g, 64%): LC/MS (Table 2, Method a) Rt=1.51 min; MS m/z: 347 (M+H)+.

1. extractionextracted with DCM (3×15 mL)
2. washThe combined organic layers were washed with brine
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. additionTo the crude material was added MeOH (˜50 mL)
7. filtrationa small amount of insoluble material (<0.01 g) was filtered
8. additionSilica gel (2 g) was added to the filtrate
9. concentrationthe mixture was concentrated under reduced pressure
10. customThe silica mixture was purified by silica gel chromatography
11. washeluting with a step-wise gradient of DCM/MeOH/NH4OH 990:9:1 to 980:18:2
12. customto give an off-white solid
13. customthat was dried in a vacuum oven at about 70° C
14. dissolutionThe solid was dissolved in hot MeOH
15. filtrationThe resulting material was filtered while hot
16. customto remove particulates
17. customThe filtrate was sonicated
18. temperaturewhile cooling
19. customto get a fine suspension which
20. concentrationwas then concentrated under reduced pressure
21. customdried in a vacuum oven at about 100° C.

ORD record

ord-d528db8f0c004fbda68d043d35d8b287

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962629B2