反应详情

To a solution of tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate (600 mg, 1.35 mmol, 1.0 equiv) in MeOH (3 mL) was added HCl (4N in dioxane, 3 mL, 12 mmol, 8.9 equiv). After 1 h, the solvent was removed in vacuo. To this residue was added DCM (10 mL) and Et3N (875 μL, 6.28 mmol, 4.65 equiv), and the resulting solution was divided into two equal parts. To the resulting solution was added methyl chloroformate (75 μL, 0.95 mmol, 1.4 equiv) dropwise by syringe. After 30 min, the reaction was quenched by the addition of aq. satd. NaHCO3. The reaction was diluted with EtOAc, and washed twice with aq. satd. NaHCO3 and once with brine. The solution was then dried over sodium sulfate, filtered and concentrated in vacuo. Purification by reverse phase preparative HPLC provided methyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate (201.3 mg, 77%). LCMS m/z (APCI)=402.2 (M+H). LCMS m/z (APCI)=402.2 (M+H).

1. customthe solvent was removed in vacuo
2. waitAfter 30 min
3. customthe reaction was quenched by the addition of aq. satd
4. additionThe reaction was diluted with EtOAc
5. washwashed twice with aq. satd
6. dry with materialThe solution was then dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customPurification by reverse phase preparative HPLC