Hydrochloric Acid → N4-{4-[(3-Cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluorophenyl}-6-(trifluoromethyl)-pyrimidine-2,4-diamine

HRID 2192196Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2192196
[CH:1]1([C:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][C:11]=3[O:13][C:14]3[C:20]([F:21])=[CH:19][C:17]([NH2:18])=[CH:16][C:15]=3[F:22])[NH:6][CH:5]=2)[CH2:3][CH2:2]1.Cl[C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[N:27]=[C:26]([NH2:34])[N:25]=1.Cl.[OH-].[Na+]>O.C(O)C>[CH:1]1([C:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][C:11]=3[O:13][C:14]3[C:15]([F:22])=[CH:16][C:17]([NH:18][C:24]4[CH:29]=[C:28]([C:30]([F:33])([F:31])[F:32])[N:27]=[C:26]([NH2:34])[N:25]=4)=[CH:19][C:20]=3[F:21])[NH:6][CH:5]=2)[CH2:3][CH2:2]1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 130869074-Chloro-6-(trifluoromethyl)pyrimidin-2-amine2×HCID 597409994-[(3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluoroaniline

Produkt 1

HCID 11496330N4-{4-[(3-Cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluorophenyl}-6-(trifluoromethyl)-pyrimidine-2,4-diamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

330 mg (1.10 mmol) of 4-[(3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3,5-difluoroaniline and 320 mg (1.64 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine are suspended in 4 ml of water and 2 ml of ethanol. 0.55 ml (2.2 mmol) of 4N hydrochloric acid is added, and the mixture is heated at reflux for 1 h. Another 107 mg (0.55 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine are then added, and the mixture is heated for a further 2 hours. The mixture is made alkaline by addition of 1N aqueous sodium hydroxide solution and extracted with ethyl acetate, and the organic phase is washed with water. The organic phase is dried over sodium sulfate and the solvent is removed under reduced pressure. The product is purified by preparative HPLC.

Aufarbeitung

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 1 h
  3. temperaturethe mixture is heated for a further 2 hours
  4. extractionextracted with ethyl acetate
  5. washthe organic phase is washed with water
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. customthe solvent is removed under reduced pressure
  8. customThe product is purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-6b4d92bc41f7442a80ceb93c1c0005f4
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08329716B2

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