反应详情

温度

-10 °C

4-Methyl-2-(3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propanoylamino) pentanoic acid (200 mg, 0.52 mmol) was dissolved in THF (1.2 mL). N-Methylmorpholine (0.057 mL, 0.52 mmol) was added, and the resulting clear solution was cooled to −10° C. Isobutyl chloroformate (0.068 mL, 0.52 mmol) was added dropwise to cause N-Methylmorpholine HCl salt precipitation. N,N′-dimethylhydrazine hydrochloride salt (346 mg, 2.6 mmol) was dissolved in 3N NaOH (1.7 mL). The resulting mixture was added to the solution and stirred for 1 h. The solution was extracted by EtOAc, and washed with 5% NaHSO3, saturated sodium bicarbonate solution, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated by rotary evaporation. Purification by chromatography (silica, 20/1: DCM/MeOH, Rf=0.3) afforded N2-[1-benzyl-2-(1-[(1,2-dimethylhydrazino) carbonyl]-3-methylbutylamino)-2-oxoethyl]-2-pyrazinecarboxamide as a pale yellow solid (197 mg, 89%).

1. customN-Methylmorpholine HCl salt precipitation
2. additionThe resulting mixture was added to the solution
3. extractionThe solution was extracted by EtOAc
4. washwashed with 5% NaHSO3, saturated sodium bicarbonate solution, and brine
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated by rotary evaporation
8. customPurification by chromatography (silica, 20/1: DCM/MeOH, Rf=0.3)