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

HRID 2192183Notes

Reaction equation

HRID 2192183 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:16][CH:17]=[C:18]([Cl:19])[C:11]=12)[NH2:5].[Cl:20][C:21]1[CH:26]=[C:25](Cl)[N:24]=[C:23]([NH2:28])[N:22]=1.Cl.[OH-].[Na+]>O.C(O)C>[Cl:20][C:21]1[N:22]=[C:23]([NH2:28])[N:24]=[C:25]([NH:5][C:4]2[CH:6]=[CH:7][C:8]([O:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]4[NH:16][CH:17]=[C:18]([Cl:19])[C:11]=34)=[C:2]([F:1])[CH:3]=2)[CH:26]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 655222-Amino-4,6-dichloropyrimidineHCID 597410163-fluoro-4-[(3-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]aniline

Product 1

HCID 115242606-Chloro-N4-{4-[(3-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-3-fluorophenyl}pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

67 mg (0.24 mmol) of 3-fluoro-4-[(3-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]aniline and 40 mg (0.24 mmol) of 4,6-dichloropyrimidine-2-amine are suspended in 4 ml of water/ethanol 1:1. 25 μl (0.29 mmol) of 37% strength hydrochloric acid are added, and the mixture is heated at reflux overnight. Using 1N aqueous sodium hydroxide solution, the pH is adjusted to 7 and the mixture is extracted with ethyl acetate. The organic phase is washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated. The residue is purified by preparative HPLC.

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux overnight
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic phase is washed with saturated sodium chloride solution
  5. dry with materialdried with magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-7207ff13af274f59abc1da01c38d75ab
Source dataset
uspto-grants-2012_12
Patent number
US08329716B2

Reaction notes

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