反应详情

To a pressure vessel was added 4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-chloro-2-pyrimidinyl]amino]benzonitrile (0.00064 mol), tetrahydrofuran (3 ml), O-methylhydroxylamine (0.06 g), tetrahydrofuran and NaOH 1N (0.00067 mol). The reaction mixture was stirred for 3 days at room temperature, then for 1 day at 75° C., for 1 day at 90° C. and for 2 days at 110° C. To O-methylhydroxylamine (0.60 g) was added tetrahydrofuran (4 ml) and NaOH 50% (0.00719 mol). The liquid was decanted into the reaction flask and the reaction mixture was heated at 110° C. for 3 days. The solvent was evaporated. The residue was dissolved in CH2Cl2, washed with a saturated NaHCO3 solution and water, dried (Na2SO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 98/2). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from CH3CN, filtered off and dried, yielding 0.15 g of 4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-(methoxyamino)-2-pyrimidinyl]amino]benzonitrile (51%); mp. 185-186° C. The sample was dried (0.2 mm Hg, 80° C., 16 hours) (comp. 48).

1. waitfor 1 day at 75° C.
2. waitfor 1 day at 90° C.
3. waitfor 2 days at 110° C
4. customThe liquid was decanted into the reaction flask
5. temperaturethe reaction mixture was heated at 110° C. for 3 days
6. customThe solvent was evaporated
7. dissolutionThe residue was dissolved in CH2Cl2
8. washwashed with a saturated NaHCO3 solution and water
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. customthe solvent was evaporated
12. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 98/2)
13. customThe pure fractions were collected
14. customthe solvent was evaporated
15. customThe residue was crystallized from CH3CN
16. filtrationfiltered off
17. customdried