Hydrochloric Acid → N-(4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide

To a flask containing tert-butyl 4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)bicyclo[2.2.2]octan-1-ylcarbamate (0.175 g, 0.327 mmol) was added a solution of HCl (4 N in 1,4-dioxane, 5 mL). After about 2 h at ambient temperature, the reaction mixture was concentrated under reduced pressure. The crude amine hydrochloride was dissolved in DCM (10 mL) and TEA (0.36 mL, 2.6 mmol) was added to the reaction mixture followed by cyclopropanesulfonyl chloride (0.18 g, 1.3 mmol). After about 2 h at ambient temperature, DMF (3 mL) was added and the reaction mixture was concentrated under reduced pressure to remove DCM. After a further about 4 h at ambient temperature, EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL) was added to the reaction mixture. The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude reaction mixture was purified by chromatography on silica gel using 20-80% EtOAc in DCM to provide N-(4-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide as a tan solid (0.025 g, 14%). LC/MS (Table 2, Method a) Rt=2.34 min; MS m/z: 540 (M+H)+.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. dissolutionThe crude amine hydrochloride was dissolved in DCM (10 mL)
3. waitAfter about 2 h at ambient temperature
4. concentrationthe reaction mixture was concentrated under reduced pressure
5. customto remove DCM
6. waitAfter a further about 4 h at ambient temperature
7. additionEtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL) was added to the reaction mixture
8. customThe organic layer was separated
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe crude reaction mixture
13. customwas purified by chromatography on silica gel using 20-80% EtOAc in DCM

ORD 기록

ord-61c76a7917b94f1796bdb1a0f48dea35

출처 데이터셋

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08962629B2