反应详情

Dissolve N-methyl acetamide (187 mg, 2.55 mmol) in dry N,N-dimethylformamide (5 mL) at room temperature under nitrogen. Add sodium hydride (60% dispersion in oil, 102 mg, 2.55 mmol), stir for 1 hr., then add 3′-(4-chloromethyl-phenyl)-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (300 mg, 0.64 mmol) and sodium iodide (96 mg, 0.64 mmol). Stir the reaction at 50° C. for 20 hr., the quench with water (10 mL). Extract with DCM (4×10 mL) and pass through an IST Phase Separator Frit®. Purify using SCX-2 chromatography, eluting with 3 M ammonia in methanol and further purify using silica gel chromatography (eluting with 5:95 methanol:DCM). Dissolve the clear oil in acetonitrile, and add 2 M aq. HCl and water then lyophilize to give the title compound as light yellow powder (87 mg, 29%). MS (ES): m/z=434 [M+H].

1. customthe reaction at 50° C. for 20 hr
2. custom, the quench with water (10 mL)
3. extractionExtract with DCM (4×10 mL)
4. customPurify
5. washeluting with 3 M ammonia in methanol
6. customfurther purify
7. washsilica gel chromatography (eluting with 5:95 methanol:DCM)
8. dissolutionDissolve the clear oil in acetonitrile
9. additionadd 2 M aq. HCl and water