反应详情

To a solution of (3S)-3-methylmorpholine hydrochloride (0.2059 g, 1.496 mmol) in DMF (7.5 mL) was added tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (0.7451 g, 1.498 mmol), and N,N-diisopropylethylamine (0.575 mL, 3.301 mmol). The solution was stirred overnight, and then diluted with Et2O (150 mL). The mixture was washed with water (2×50 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (50 mL). This Et2O layer was washed with a fresh portion of water (50 mL), and the combined organic phase was diluted with DCM (50 mL), dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and azeotroped with EtOAc. The solid was collected by vacuum filtration and washed with hexanes. The supernatant was concentrated in vacuo, and purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N). The desired fractions were concentrated in vacuo, and the resulting solid was collected by vacuum filtration, washed with hexanes, and combined with the first crop of solid to give tris(1,1-dimethylethyl)2-{2-chloro-5-fluoro-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (0.6610 g, 79%) as a white solid. LCMS: (M+H)+: 562.2.

1. washThe mixture was washed with water (2×50 mL)
2. extractionthe combined aqueous phase was extracted with a fresh portion of Et2O (50 mL)
3. washThis Et2O layer was washed with a fresh portion of water (50 mL)
4. additionthe combined organic phase was diluted with DCM (50 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customazeotroped with EtOAc
9. filtrationThe solid was collected by vacuum filtration
10. washwashed with hexanes
11. concentrationThe supernatant was concentrated in vacuo
12. custompurified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N)
13. concentrationThe desired fractions were concentrated in vacuo
14. filtrationthe resulting solid was collected by vacuum filtration
15. washwashed with hexanes