Nitrogen → HCID 58557614, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of phosgene (0.400 mL, 0.761 mmol, 20% in toluene) in DCM (1.5 mL) under a balloon of N2 at about 0° C. were added a solution of 1-((cis)-4-ethylpyrrolidin-3-yl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.250 g, 0.609 mmol, Example #36, step F) in DCM (5.0 mL) and TEA (0.430 mL, 3.08 mmol). After about 40 min, at about 0° C., a solution of 3,3-difluoroazetidine•hydrochloride (0.095 g, 0.731 mmol, Matrix) and TEA (0.430 mL, 3.08 mmol) in DCM (5.0 mL) were added dropwise and stirred at about 0° C. for about 45 min. Saturated aqueous sodium bicarbonate (2 mL) was added and the layers were separated. The aqueous layer was extracted with DCM (2×30 mL). The combined organic layers were washed with water (25 mL), dried over anhydrous MgSO4, filtered, and concd to give a brown residue. The crude material was purified via flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM to afford (3,3-difluoroazetidin-1-yl)((cis)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)pyrrolidin-1-yl)methanone (0.208 g, 65%) as a brown residue: LC/MS (Table 1, Method a) Rt=2.17 min; MS m/z: 530 (M+H)+.

Provenance & Evidence