反应详情

温度

60 °C

Methyl 3-((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)amino)-2,2-difluoropropanoate, was dissolved in AcOH (10 mL). Iron powder (224 mg, 4 mmol) was added followed by the slow addition of HCl (1.5 mL, conc.). The reaction mixture was left to stir at 60° C. for 1 hr. The reaction was then cooled, the stir bar and unreacted iron removed by filtration through paper, and the solvent volume reduced by about 75% on a rotovap. The mixture was then diluted with ice water and EtOAc. Aqueous layer basified by careful addition of sat. NaHCO3. The organic extracts combined, dried over MgSO4, filtered and concentrated to yield 2-chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one as a brown syrup (550 mg) which was used directly for next step without further purification. [M+H] calc'd for C12H13ClF2N4O, 303; found 303.

1. waitThe reaction mixture was left
2. temperatureThe reaction was then cooled
3. customthe stir bar and unreacted iron removed by filtration through paper
4. additionThe mixture was then diluted with ice water and EtOAc
5. additionAqueous layer basified by careful addition of sat. NaHCO3
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated