反应详情

To a solution of KOH (224 mg, 4.0 mmol) and CH3OH (10 mL) is added 1-[(R)-4-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)2-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-yl)-ethanone (400 mg, 1.0 mmol) in CH3OH (10 mL) and then iodobenzene diacetate (464 mg, 1.5 mmole) in portions at 0° C. The mixture is stirred at room temperature overnight. The solvent is removed and then extracted with DCM. The organic layer is washed with aqueous NH4Cl and afterwards concentrated to yield crude example 112. This material is dissolved in water and then 6 N HCl (5 mL) is added. The mixture is stirred at room temperature for 3 h. Afterwards it is made basic with NaHCO3 and extracted with DCM. The organic layer is concentrated to give a crude product that is purified by chromatography on silica gel (EtOAc/Heptane: 50%˜100%) to give the title compound (240 mg, 58%) as a yellow solid.

1. customat 0° C
2. customThe solvent is removed
3. extractionextracted with DCM
4. washThe organic layer is washed with aqueous NH4Cl
5. concentrationafterwards concentrated
6. customto yield crude example 112
7. stirringThe mixture is stirred at room temperature for 3 h
8. extractionextracted with DCM
9. concentrationThe organic layer is concentrated
10. customto give a crude product that
11. customis purified by chromatography on silica gel (EtOAc/Heptane: 50%˜100%)