3,3,3-Trifluoropropane-1-sulfonyl chloride → HCID 53257535, compound

Participants

Reaction Steps

To slurry of palladium hydroxide on carbon (20 mol %, 0.013 g, 0.019 mmol) in EtOH (5 mL) was added a solution of 1-((2R,4S)-4-azido-2-ethylpyrrolidin-1-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.110 g, 0.371 mmol, prepared using E from (2R,4S)-tert-butyl-4-azido-2-ethylpyrrolidine-1-carboxylate (synthesized as described in. J. Med. Chem. 1988, 31, 1598-1611) with HCl, J with Example #5, Step C, OO, D with NaOH) in EtOH (2 mL). The reaction mixture was sparged with hydrogen and an atmosphere of hydrogen was maintained via balloon. After about 2 h the reaction mixture was filtered and concd under reduced pressure The residue was dissolved in DCM (5 mL) and 3,3,3-trifluoropropane-1-sulfonyl chloride (0.080 g, 0.41 mmol, Matrix) was added. After about 15 h additional 3,3,3-trifluoropropane-1-sulfonyl chloride (80 mg, 0.408 mmol, Matrix) was added. After about 2 days the reaction mixture was partitioned between EtOAc (10 mL) and brine (10 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concd under reduced pressure. The crude product was purified by chromatography on silica gel eluting with EtOAc to provide N-((3S,5R)-5-ethyl-1-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)pyrrolidin-3-yl)-3,3,3-trifluoropropane-1-sulfonamide (0.025 g, 16%) as a brown solid: LC/MS (Table 1, Method a) Rt=1.81 min; MS m/z: 431 (M+H)+.

Provenance & Evidence