反应详情

Dissolve succinimide (99 mg, 1.0 mmol) in dry DCM (5 mL) under nitrogen. Add triphenylphosphine (408 mg, 1.5 mmol) and stir for 20 min. at room temperature. Add {4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-methanol (378 mg, 1.0 mmol) and diethyl azodicarboxylate (0.19 mL, 1.1 mmol) and stir for 20 hr. Add water (10 mL), extract with DCM (2×5 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify by SCX-2® chromatography washing with methanol then eluting with 2 M ammonia in methanol. Further purify (silica gel chromatography, eluting with 0:100 to 5:95 methanol:DCM), to give the free base as a light yellow oil. Purify again by low pH reverse phase HPLC, and form the free base by passing through an SCX-2® ion exchange cartridge washing with methanol then eluting with 3.5 M ammonia in methanol. Dissolve the oil in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a yellow powder (127 mg, 26%). MS (ES): m/z=460 [M+H]+.

1. extractionAdd water (10 mL), extract with DCM (2×5 mL)
2. concentrationconcentrate
3. custompurify by SCX-2® chromatography
4. washwashing with methanol
5. washthen eluting with 2 M ammonia in methanol
6. customFurther purify
7. wash(silica gel chromatography, eluting with 0:100 to 5:95 methanol:DCM)