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

HRID 2192185Notes

Reaction equation

HRID 2192185 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[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][C:15]=3[F:21])[NH:6][CH:5]=2)[CH2:3][CH2:2]1.Cl[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[N:26]=[C:25]([NH2:33])[N:24]=1.Cl.[OH-].[Na+]>O>[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[CH:20]=[CH:19][C:17]([NH:18][C:23]4[CH:28]=[C:27]([C:29]([F:32])([F:30])[F:31])[N:26]=[C:25]([NH2:33])[N:24]=4)=[CH:16][C:15]=3[F:21])[NH:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 130869074-Chloro-6-(trifluoromethyl)pyrimidin-2-amine2×HCID 597410174-[(3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluoroaniline

Product 1

HCID 11690823N4-{4-[(3-Cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluorophenyl}-6-(trifluoromethyl)pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

114 mg (0.40 mmol) of 4-[(3-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluoroaniline and 95 mg (0.48 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine are suspended in 3.5 ml of water. 0.52 ml (0.52 mmol) of 1N hydrochloric acid are added, and the mixture is heated at reflux overnight. Another 30 mg (0.15 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine are then added, and the mixture is heated for another 6 hours. By addition of 1N aqueous sodium hydroxide solution, the pH is adjusted to 10, resulting in the precipitation of crystals. The crystals are filtered off with suction and purified by chromatography on silica gel (mobile phase: dichloromethane/methanol (7N ammonia) 100:1 to 100:3).

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux overnight
  3. temperaturethe mixture is heated for another 6 hours
  4. customresulting in the precipitation of crystals
  5. filtrationThe crystals are filtered off with suction
  6. custompurified by chromatography on silica gel (mobile phase: dichloromethane/methanol (7N ammonia) 100:1 to 100:3)

Sources & evidence

ORD record
ord-12377dd186ee482bb37391b3a8b567ff
Source dataset
uspto-grants-2012_12
Patent number
US08329716B2

Reaction notes

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