O-Methylhydroxylamine → 4-[[5-Bromo4-(4-cyano-2,6-dimethylphenoxy)-6-(methoxyamino)-2-pyrimidinyl]amino]benzonitrile

HRID 41371

Reaktionsgleichung

Reaktionsgleichung von HRID 41371
[Br:1][C:2]1[C:3]([O:18][C:19]2[C:24]([CH3:25])=[CH:23][C:22]([C:26]#[N:27])=[CH:21][C:20]=2[CH3:28])=[N:4][C:5]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[N:6][C:7]=1Cl.[CH3:29][O:30][NH2:31].[OH-].[Na+]>O1CCCC1>[Br:1][C:2]1[C:3]([O:18][C:19]2[C:24]([CH3:25])=[CH:23][C:22]([C:26]#[N:27])=[CH:21][C:20]=2[CH3:28])=[N:4][C:5]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[N:6][C:7]=1[NH:31][O:30][CH3:29]

Komponenten

5

Edukt 3

HCID 4113O-Methylhydroxylamine2×HCID 14798Sodium Hydroxide2×HCID 117514166-Desamino 6-Chloro Etravirine

Produkt 1

HCID 221701054-[[5-Bromo4-(4-cyano-2,6-dimethylphenoxy)-6-(methoxyamino)-2-pyrimidinyl]amino]benzonitrileAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-1062923dc01f41609620fe157f40049c
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530655B2

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