反应详情

温度

0 °C

To a 0° C. solution of triphosgene (150 mg, 0.50 mmol, 0.35 equiv) in THF (15 mL) was slowly added via cannula a solution of (R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylate (500 mg, 1.4 mmol, 1.0 equiv) and DIPEA (485 μL, 18.5 mmol, 2.0 equiv) in THF (15 mL) over approximately 15 minutes. The solution was stirred for an additional 20 min at 0° C., and 4-amino-2-methylpyridine was then added. After stirring at room temperature overnight, the reaction was diluted with EtOAc, washed with aq. satd. NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated in vacuo. Purification by reverse phase preparative HPLC provided (R)-benzyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate (180 mg, 27%). LCMS m/z (APCI)=492.3 (M+H).

1. stirringAfter stirring at room temperature overnight
2. washwashed with aq. satd
3. dry with materialNaHCO3 and brine, dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification by reverse phase preparative HPLC