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

Participants

Reaction Steps

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)+.

Provenance & Evidence