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

HRID 2192187Notes

Reaction equation

HRID 2192187 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][C:10]=2[O:12][C:13]2[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][C:14]=2[F:20])[NH:5][CH:4]=1)[CH3:2].N1C=CC=NC=1N.Cl.Cl[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[N:33]=[C:32]([NH2:40])[N:31]=1.[OH-].[Na+]>O>[CH2:1]([C:3]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][C:10]=2[O:12][C:13]2[CH:19]=[CH:18][C:16]([NH:17][C:30]3[CH:35]=[C:34]([C:36]([F:39])([F:37])[F:38])[N:33]=[C:32]([NH2:40])[N:31]=3)=[CH:15][C:14]=2[F:20])[NH:5][CH:4]=1)[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric Acid2×HCID 79782-AminopyrimidineHCID 14798Sodium HydroxideHCID 130869074-Chloro-6-(trifluoromethyl)pyrimidin-2-amineHCID 597410004-[(3-Ethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluoroaniline

Product 1

HCID 11502907N4-{4-[(3-Ethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluorophenyl}-6-(trifluoromethyl)pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

45 mg (0.17 mmol) of 4-[(3-ethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluoroaniline and 34 mg (0.17 mmol) of 4-chloro-6-trifluoromethyl)pyrimidine-2-amine are suspended in 5 ml of water. 24 μl of 37% strength hydrochloric acid are added, and the mixture is heated at reflux overnight. Another 70 mg (0.35 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine and 40 μl of 37% strength hydrochloric acid are then added, and the mixture is heated at reflux for another night. Using 1N aqueous sodium hydroxide solution, the pH is then adjusted to 10. The mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel (mobile phase: dichloromethane/methanol 100:1 to 10:1). The product obtained is purified further by preparative HPLC.

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux overnight
  3. temperaturethe mixture is heated
  4. temperatureat reflux for another night
  5. concentrationThe mixture is concentrated under reduced pressure
  6. customthe residue is purified by column chromatography on silica gel (mobile phase: dichloromethane/methanol 100:1 to 10:1)
  7. customThe product obtained
  8. customis purified further by preparative HPLC

Sources & evidence

ORD record
ord-5ea1cb1abebe4314b1481cb153e23b57
Source dataset
uspto-grants-2012_12
Patent number
US08329716B2

Reaction notes

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