5-Hydroxyindole → 4-Chloro-6-(1H-5-indolyloxy)-2-pyrimidinamine

HRID 2376813Notes

Reaction equation

HRID 2376813 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2.[NH2:13][C:14]1[N:19]=[C:18](Cl)[CH:17]=[C:16]([Cl:21])[N:15]=1>CS(C)=O>[Cl:21][C:16]1[CH:17]=[C:18]([O:3][C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][CH:12]=2)[NH:9][CH:8]=[CH:7]3)[N:19]=[C:14]([NH2:13])[N:15]=1

Participants

5

Reactant 3

HCID 160545-HydroxyindoleHCID 24758Sodium hydrideHCID 655222-Amino-4,6-dichloropyrimidine

Product 1

HCID 219493934-Chloro-6-(1H-5-indolyloxy)-2-pyrimidinamineYield 22.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Sodium hydride (1.0 g, 25 mmol) was suspended in dimethyl sulfoxide (40 ml) under nitrogen atmosphere, and 5-hydroxyindole (3.33 g, 25 mmol) was gradually added while the reaction mixture was stirred at room temperature. After 20 minutes, 2-amino-4,6-dichloropyrimidine (3.28 g, 20 mmol) was added. The reaction mixture was heated at 100° C. and was stirred for 3 hours. After the reaction mixture was cooled to room temperature, the reaction mixture was partitioned between ethyl acetate and 10% aqueous ammonia solution. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. After the solvent was distilled off, the residue was purified by NH silica gel column chromatography (eluent; ethyl acetate:hexane=2:1). The crystals were precipitated from ethyl acetate, filtered off, and dried under aeration to yield the title compound (1.15 g, 4.41 mmol, 22.0%) as white crystals.

Workup

  1. temperatureThe reaction mixture was heated at 100° C.
  2. stirringwas stirred for 3 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. customthe reaction mixture was partitioned between ethyl acetate and 10% aqueous ammonia solution
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationAfter the solvent was distilled off
  8. customthe residue was purified by NH silica gel column chromatography (eluent; ethyl acetate:hexane=2:1)
  9. customThe crystals were precipitated from ethyl acetate
  10. filtrationfiltered off
  11. customdried under aeration

Sources & evidence

ORD record
ord-b6d366d6367044f98065a93b54b265d7
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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