反应详情

温度

0 °C

To a 0° C. cooled solution of (E)-4-fluoro-N-(6-(hydroxymethyl)-1-(cis-4-isobutyramidocyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide (75 mg, 0.166 mmol) in DCM (5 mL) was added thionyl chloride (0.060 mL, 0.829 mmol) dropwise. The resulting mixture was stirred at 0° C. for 30 minutes. After 30 minutes, the solvent was removed, and the residue was suspended in ACN (5 mL) and re-concentrated to remove residual thionyl chloride. The residue was resuspended in ACN (3 mL), cooled to 0° C., and 2-(piperidin-4-yl)propan-2-ol (95 mg, 0.663 mmol) was added. The reaction was stirred overnight at RT. After 16 hours, the reaction mixture was concentrated and partitioned between EtOAc and water. The organic layer was concentrated and the residue was purified by column chromatography, eluting with 0-100% (90:9:1 DCM/MeOH/NH4OH) in DCM to provide (E)-4-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-(cis-4-isobutyramidocyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as a white powder (30 mg, 31.3% yield). MS, m/z (C33H44FN5O3): calcd, 577.3. found, 578.1 [M+H].

1. waitAfter 30 minutes
2. customthe solvent was removed
3. concentrationre-concentrated
4. customto remove residual thionyl chloride
5. temperaturecooled to 0° C.
6. stirringThe reaction was stirred overnight at RT
7. waitAfter 16 hours
8. concentrationthe reaction mixture was concentrated
9. custompartitioned between EtOAc and water
10. concentrationThe organic layer was concentrated
11. customthe residue was purified by column chromatography
12. washeluting with 0-100% (90:9:1 DCM/MeOH/NH4OH) in DCM