Hydrochloric Acid → 2-[4-(4-{[2-Amino-6-(trifluoromethyl)pyrimidin-4-yl]amino}-2-fluorophenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]ethanol

HRID 2192189Notes

Reaction equation

HRID 2192189 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[NH:13][CH:14]=[C:15]([CH2:16][CH2:17][OH:18])[C:8]=23)=[C:4]([F:21])[CH:3]=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>[NH2:33][C:25]1[N:24]=[C:23]([NH:1][C:2]2[CH:20]=[CH:19][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[NH:13][CH:14]=[C:15]([CH2:16][CH2:17][OH:18])[C:8]=34)=[C:4]([F:21])[CH:3]=2)[CH:28]=[C:27]([C:29]([F:32])([F:30])[F:31])[N:26]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 130869074-Chloro-6-(trifluoromethyl)pyrimidin-2-amineHCID 210815442-[4-(4-Amino-2-fluorophenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]ethanol

Product 1

HCID 115685642-[4-(4-{[2-Amino-6-(trifluoromethyl)pyrimidin-4-yl]amino}-2-fluorophenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]ethanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

130 mg (0.45 mmol) of 2-[4-(4-amino-2-fluorophenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]ethanol and 107 mg (0.54 mmol) of 4-chloro-6-(trifluoromethyl)pyrimidine-2-amine are suspended in 6 ml of water. 0.6 ml (0.6 mmol) of 1N hydrochloric acid is added and the mixture is heated at reflux overnight. Using 1N aqueous sodium hydroxide solution, the suspension is adjusted to pH 10, resulting in the precipitation of crystals. The crystals are filtered off with suction, washed with water and purified by column 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. customresulting in the precipitation of crystals
  4. filtrationThe crystals are filtered off with suction
  5. washwashed with water
  6. custompurified by column chromatography on silica gel (mobile phase: dichloromethane/methanol (7N ammonia) 100:1 to 100:3)

Sources & evidence

ORD record
ord-d9b8eaf46d2a478ca7e90dc260c92958
Source dataset
uspto-grants-2012_12
Patent number
US08329716B2

Reaction notes

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