azetidine-1-sulfonyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (0.200 g, 0.471 mmol, Example #8, Step M) and DMF (4 mL). The solution was cooled to about 0° C. followed by the addition of TEA (0.16 mL, 1.2 mmol) and azetidine-1-sulfonyl chloride (0.165 g, 1.06 mmol, Preparation #CC.1). The reaction mixture was warmed to ambient temperature and was stirred for about 2 h. The solvent was removed under reduced pressure and DCM (10 mL) was added to the resulting residue. The organic solution was washed with water and brine (5 mL each). The combined organics were dried over anhydrous MgSO4, filtered, and concd under reduced pressure to give a brown oil. The crude material was purified by silica gel chromatography eluting with a gradient of 0-70% EtOAc in DCM to afford 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)azetidine-1-sulfonamide (0.20 g, 77%) as a white solid: LC/MS (Table 1, Method a) Rt=2.39 min; MS m/z: 544 (M+H)+. The reaction mixture was warmed to ambient temperature The solvent was removed under reduced pressure and DCM (10 mL) was added to the resulting residue The organic solution was washed with water and brine (5 mL each) The combined organics were dried over anhydrous MgSO4 filtered concd under reduced pressure to give a brown oil The crude material was purified by silica gel chromatography eluting with a gradient of 0-70% EtOAc in DCM