反应详情

Tetrapropylammonium perruthenate (1.05 g, 2.99 mmol) was added to a heterogenous mixture of tert-butyl (3-((5-(1-hydroxyethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (22.5 g, 59.8 mmol) and 4-methylmorpholine N-oxide (8.75 g, 74.7 mmol) in DCM (460 mL) at RT. The mixture was stirred at RT for 3 h and concentrated under reduced pressure. The dark solid was dissolved in 10% MeOH in DCM and the material was adsorbed on to silica gel. The material was purified by silica gel pad (2-L sintered medium frit filled halfway with silica gel) eluted with 10% EtOAc in DCM (2 L) followed by 20% EtOAc in DCM (2 L). The fractions containing the desired product was concentrated to afford a white solid. 1.2 L of 1/1 MeOH/EtOAc was added to the solid and the mixture was heated to reflux and cooled to RT slowly. The mixture sat at RT overnight. The white fluffy needles were collected by filtration and washed with EtOAc to afford tert-butyl (3-((5-acetyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (53) (12.66 g, 33.8 mmol, 56% yield). The filtrate was concentrated and the residue was absorbed on to silica gel and the material was purified by silica gel pad (2 L sintered medium frit filled halfway with silica gel) eluted with 10% EtOAc in DCM (2 L) followed by 15% EtOAc in DCM (2 L) followed by 20% EtOAc in DCM. The fractions containing the desired product was concentrated to afford a white solid. 600 mL of 1/1 MeOH/EtOAc was added to the solid and the mixture was heated to reflux and cooled to RT slowly. The mixture was seeded with a small amount of the desired product when the mixture was at 60° C. The mixture sat at RT overnight. The white fluffy needles were collected by filtration and washed with EtOAc to afford additional tert-butyl (3-((5-acetyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (53) (4.20 g, 11.22 mmol, 18% yield). m/z (ESI, +ve ion) 374.9 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 11.30 (1H, s), 8.68-8.73 (1H, m), 7.91 (1H, s), 7.30-7.35 (1H, m), 7.05 (1H, dd, J=8.0, 1.0 Hz), 6.46 (1H, br. s.), 2.59 (3H, s), 2.56 (3H, s), 1.52 (9H, s).

1. concentrationconcentrated under reduced pressure
2. dissolutionThe dark solid was dissolved in 10% MeOH in DCM
3. customThe material was purified by silica gel pad (2-L sintered medium frit filled halfway with silica gel)
4. washeluted with 10% EtOAc in DCM (2 L)
5. additionThe fractions containing the desired product
6. concentrationwas concentrated
7. customto afford a white solid
8. temperaturethe mixture was heated
9. temperatureto reflux
10. temperaturecooled to RT slowly
11. waitThe mixture sat at RT overnight
12. filtrationThe white fluffy needles were collected by filtration
13. washwashed with EtOAc