Methanesulfonamide → 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluoro-N-(methylsulfonyl)benzamide

To a solution of methanesulfonamide (26 mg, 0.28 mmol) in THF (2 mL) was added potassium tert-butoxide (32 mg, 0.28 mmol) and the mixture was stirred for 10 minutes at room temperature. A solution of 4-methylphenyl 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoate (Preparation 230, 108 mg, 0.21 mmol) in THF (2 mL) was added and the mixture was stirred at 50° C. for 10 hours. The reaction mixture was allowed to cool to room temperature. The reaction was quenched with water and acidified with 1N aqueous citric acid solution. The mixture was extracted with DCM (3×5 mL) and filtered using a phase separation cartridge. The filtrate was concentrated in vacuo to give a crude product that was purified by silica gel chromatography eluting with 0-100% EtOAc in heptane to give a product mixture as a white solid. The solid was purified by reverse phase column chromatography eluting with 5-95% CH3CN in water to give a white solid that was further purified using trituration with heptanes/acetone 9/1 to give the title compound (28 mg, 27%) as a white solid.

1. stirringthe mixture was stirred at 50° C. for 10 hours
2. temperatureto cool to room temperature
3. customThe reaction was quenched with water
4. extractionThe mixture was extracted with DCM (3×5 mL)
5. filtrationfiltered
6. customa phase separation cartridge
7. concentrationThe filtrate was concentrated in vacuo
8. customto give a crude product that
9. customwas purified by silica gel chromatography
10. washeluting with 0-100% EtOAc in heptane
11. customto give a product mixture as a white solid
12. customThe solid was purified by reverse phase column chromatography
13. washeluting with 5-95% CH3CN in water
14. customto give a white solid
15. customthat was further purified

ORD 기록

ord-364608da711b47309a8e10064f54f110

출처 데이터셋

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08592629B2