Azetidine-1-sulfonyl chloride → 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

Temperature

0 °C

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)+.

1. temperatureThe reaction mixture was warmed to ambient temperature
2. customThe solvent was removed under reduced pressure and DCM (10 mL)
3. additionwas added to the resulting residue
4. washThe organic solution was washed with water and brine (5 mL each)
5. dry with materialThe combined organics were dried over anhydrous MgSO4
6. filtrationfiltered
7. customconcd under reduced pressure to give a brown oil
8. customThe crude material was purified by silica gel chromatography
9. washeluting with a gradient of 0-70% EtOAc in DCM

ORD record

ord-129fd2de768541c19d2d139f6028c96f

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2