Reaction #69649

Reaction equation

4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-chloro-2-pyrimidinyl]amino]benzonitrile

O-methylhydroxylamine

NaOH

O-methylhydroxylamine

NaOH

→

4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-(methoxyamino)-2-pyrimidinyl]amino]benzonitrile

Yield 51.0%

Solvents

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.WAITfor 1 day at 75° C.
2. 2
   workup.WAITfor 1 day at 90° C.
3. 3
   workup.WAITfor 2 days at 110° C
4. 4
   OtherThe liquid was decanted into the reaction flask
5. 5
   Temperaturethe reaction mixture was heated at 110° C. for 3 days
6. 6
   OtherThe solvent was evaporated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in CH2Cl2
8. 8
   Washwashed with a saturated NaHCO3 solution and water
9. 9
   Dryingdried (Na2SO4)
10. 10
    Filtrationfiltered
11. 11
    Otherthe solvent was evaporated
12. 12
    OtherThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 98/2)
13. 13
    OtherThe pure fractions were collected
14. 14
    Otherthe solvent was evaporated
15. 15
    OtherThe residue was crystallized from CH3CN
16. 16
    Filtrationfiltered off
17. 17
    Otherdried

Procedure

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).

Source