反应详情

温度

0 °C

To a solution of cis-4-(5-(hydroxymethyl)-2-nitrophenylamino)-N-isopropylcyclohexanecarboxamide (3.75 g, 11.18 mmol) in DCM (127 mL) at 0° C. was added thionyl chloride (4.08 mL, 55.9 mmol) dropwise. The reaction was stirred at 0° C. for 3 hours and then at RT for 2 hours. The reaction was concentrated in vacuo and suspended in ACN and re-concentrated to remove residual thionyl chloride. The residue was resuspended in ACN (102 mL, 11.18 mmol), cooled to 0° C., and to it was added 2-(piperidin-4-yl)propan-2-ol (5.60 g, 39.1 mmol). The reaction was stirred at RT overnight. The mixture was filtered, and the filtrate concentrated in vacuo. The residual material was purified via silica gel chromatography, eluting with 90:10:1 DCM:MeOH:NH4OH to provide cis-4-(5-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-2-nitrophenylamino)-N-isopropylcyclohexanecarboxamide (4.64 g, 10.07 mmol, 90% yield) as an orange solid. MS m/z=461.4 [M+H], calc 460.61 for C25H40N4O4.

1. waitat RT for 2 hours
2. concentrationThe reaction was concentrated in vacuo
3. concentrationre-concentrated
4. customto remove residual thionyl chloride
5. temperaturecooled to 0° C.
6. stirringThe reaction was stirred at RT overnight
7. filtrationThe mixture was filtered
8. concentrationthe filtrate concentrated in vacuo
9. customThe residual material was purified via silica gel chromatography
10. washeluting with 90:10:1 DCM