Dimethyl Sulfone → 1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-2-methanesulfonyl-ethanol

To a solution of methyl sulfone (65 mg, 0.68 mmol) in THF (1.5 mL) is added a solution of n-BuLi (0.27 mL, 0.68 mmol, 2.5 M solution in hexane) at −78° C. After stirring for 5 minutes, HMPA (0.1 mL) is added. After stirring for additional 10 minutes, a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (26 mg, 0.069 mmol) in THF (1 mL) is added. The resulting solution is stirred for 1.5 hours at −78° C. The reaction is quenched with saturated aqueous NH4Cl, warmed to room temperature, and diluted with EtOAc. The organic layer is washed with water, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (3% MeOH in CH2Cl2) to give the crude desired product (31 mg, 96%) which is used directly without further purification: MS APCI (+) m/z 462, 464 (M+, Br pattern) detected.

1. stirringAfter stirring for additional 10 minutes
2. stirringThe resulting solution is stirred for 1.5 hours at −78° C
3. customThe reaction is quenched with saturated aqueous NH4Cl
4. additiondiluted with EtOAc
5. washThe organic layer is washed with water
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. custompurified by flash chromatography (3% MeOH in CH2Cl2)

ORD 기록

ord-339d876b24a643c6b06b5a50bc710c57

출처 데이터셋

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07425637B2