反应详情

温度

80 °C

Silver trifluoromethanesulphonate (9.39 g, 36.56 mmol) was added in a single batch to a solution of (3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one (which may be prepared as described in Description 14a) (71 g, 182.81 mmol) in MeCN (1000 mL) and the reaction was heated at 80° C. for 22 hours. The solvent was evaporated and the residue dissolved in DCM (1000 mL). Saturated NaHCO3 (500 ml) and water (500 ml) were added and the mixture shaken. The phases were separated and the organic layer treated with a solution of cysteine (100 g, 825.35 mmol) in water (1500 ml). This mixture was stirred vigorously for 30 minutes. The mixture was filtered through a pad of celite, and the celite washed with DCM (2×100 ml). The phases were separated and the organic layer placed in a large beaker. To this was added a solution of cysteine (50 g, 412.68 mmol) in water (500 ml) and the mixture was stirred for a further 30 minutes. The phases were separated and the organic layer was washed with a mixture of sat. brine (500 ml) and water (500 ml). The organic layer was dried (MgSO4) and the solvent evaporated to afford a dark brown foam. To the foam was added acetone (50 ml) and almost immediately a thick precipitate formed. This was swirled for about 5 minutes prior to slow addition of Et2O (150 ml) over approx. 10 minutes. After addition, the suspension was left to stand for 30 minutes. The solid was filtered off and washed with ether (3×30 ml) to afford the title material as a light brown solid (D15a) (49.24 g), pure by NMR and consistent with that produced by Method 1;

1. customThe solvent was evaporated
2. dissolutionthe residue dissolved in DCM (1000 mL)
3. additionSaturated NaHCO3 (500 ml) and water (500 ml) were added
4. customThe phases were separated
5. stirringThis mixture was stirred vigorously for 30 minutes
6. filtrationThe mixture was filtered through a pad of celite
7. washthe celite washed with DCM (2×100 ml)
8. customThe phases were separated
9. stirringthe mixture was stirred for a further 30 minutes
10. customThe phases were separated
11. washthe organic layer was washed with a mixture of sat. brine (500 ml) and water (500 ml)
12. dry with materialThe organic layer was dried (MgSO4)
13. customthe solvent evaporated
14. customto afford a dark brown foam
15. customalmost immediately a thick precipitate formed
16. additionAfter addition
17. waitthe suspension was left
18. waitto stand for 30 minutes
19. filtrationThe solid was filtered off
20. washwashed with ether (3×30 ml)