反应详情

温度

60 °C

A mixture of 3-(4-methyl-1-piperazinyl)-2(1H)-pyrazinone (obtained in Step 2 above; 0.5 g, 2.6 mmol) and t-BuOK (440 mg, 3.90 mmol) in THF (40 mL) was stirred until the mixture became thick (about 10 min), and then a solution of 2-(2,4,5-trifluorophenoxy)ethyl methanesulfonate (0.90 g, 2.2 mmol; from Step 4) in THF (10 mL) was added. After being stirred for 5 days at ambient temp, HPLC showed only 50% conversion. The reaction solution was then heated to 60° C. overnight which gave almost full conversion. The reaction was worked up according to the following: water was added, THF was evaporated off and the aqueous mixture was extracted twice with EtOAc, dried (Na2SO4) and concentrated to yield 1.08 g of the crude product as a yellow oil. Purification by chromatography on silica gel [eluent: 2% MeOH in CHCl3+NH3 (g)] gave the title compound as a yellow oil, which solidified upon cooling. Yield: 304 mg (32%). HPLC purity: 100%. MS m/z 369 (M+H)+. HRMS m/z calcd for C17H19F3N4O2 (M)+ 368.1460, found 368.1462.

1. custom(about 10 min)
2. stirringAfter being stirred for 5 days at ambient temp
3. customgave almost full conversion
4. additionwas added
5. customTHF was evaporated off
6. extractionthe aqueous mixture was extracted twice with EtOAc
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. customto yield 1.08 g of the crude product as a yellow oil
10. customPurification by chromatography on silica gel [eluent: 2% MeOH in CHCl3+NH3 (g)]