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 2192196Notes

Reaction equation

HRID 2192196 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6b4d92bc41f7442a80ceb93c1c0005f4
Source dataset
uspto-grants-2012_12
Patent number
US08329716B2

Reaction notes

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