Methanol → 1-(3-Bromophenyl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amine

n-Butyllithium (0.254 mL, 0.63 mmol) was dropwise added to 4-bromo-2-(difluoromethyl)pyridine (120 mg, 0.58 mmol) in anhydrous THF (5.00 mL) at −78° C. under argon atmosphere. The reaction mixture was stirred for 25 min. N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (235 mg, 0.58 mmol) in anhydrous THF (5.00 mL) was dropwise added. The reaction mixture was stirred for 2 h, then methanol (5 mL) was added and the temperature was allowed to reach room temperature. The reaction mixture was partitioned between aqueous ammonium chloride and ethyl acetate. The aqueous phase was extracted with ethyl acetate (×3). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by prep. HPLC to afford the title compound (47.1 mg, 18%).

1. stirringThe reaction mixture was stirred for 2 h
2. customto reach room temperature
3. customThe reaction mixture was partitioned between aqueous ammonium chloride and ethyl acetate
4. extractionThe aqueous phase was extracted with ethyl acetate (×3)
5. dry with materialThe combined organic layers were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by prep

ORD 기록

ord-6efaf476fe7c41658f2105da209f2890

출처 데이터셋

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08030500B2