反应详情

Dissolve {4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-methanol (200 mg, 0.53 mmol) in DCM (5 mL) at room temperature under nitrogen. Add carbonyl diimidazole (94 mg, 0.58 mmol) and stir for 20 hr. Add a solution of methylamine in tetrahydrofuran (2 M, 2 mL, 4.0 mmol) and stir reaction for 2 hr. at room temperature. Quench reaction with water (10 mL) then extract with DCM (2×10 mL), pass through an IST Phase Separator Frit® and concentrate. Purify 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 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 (28 mg, 12%). MS (ES): m/z=436 [M+H]+

1. customreaction for 2 hr
2. customat room temperature
3. customQuench
4. customreaction with water (10 mL)
5. extractionthen extract with DCM (2×10 mL)
6. concentrationconcentrate
7. customPurify by low pH reverse phase HPLC
8. customform the free base
9. washwashing with methanol
10. washthen eluting with 3 M ammonia in methanol
11. dissolutionDissolve the oil in acetonitrile
12. additionby adding 2 M aq HCl solution