Potassium Carbonate → N-[(2,4-dimethoxyphenyl)methyl]pyrimidin-2-amine

HRID 2203445Notes

Reaction equation

HRID 2203445 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl[C:8]1[N:13]=[CH:12][CH:11]=[CH:10][N:9]=1.[CH3:14][O:15][C:16]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:17]=1[CH2:18][NH2:19]>C(#N)C>[CH3:14][O:15][C:16]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:17]=1[CH2:18][NH:19][C:8]1[N:13]=[CH:12][CH:11]=[CH:10][N:9]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 744042-ChloropyrimidineHCID 5972502,4-Dimethoxybenzylamine

Product 1

HCID 55026262N-[(2,4-dimethoxyphenyl)methyl]pyrimidin-2-amineYield 84%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Potassium carbonate (2.97 g, 21.5 mmol) was added to a mixture of 2-chloropyrimidine (2.1 g, 17.9 mmol), 2,4-dimethoxybenzylamine (3.0 g, 17.9 mmol) and acetonitrile (20 mL). The reaction mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and partitioned between ethyl acetate (150 mL) and water (10 mL). The organic phase was washed with water (2 10 mL) and brine (10 mL), dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was triturated in diethyl ether (20 mL), washed with hexanes (20 mL) and purified by column chromatography, eluting with a 0-100% gradient of ethyl acetate in hexanes to afford N-(2,4-dimethoxybenzyl)pyrimidin-2-amine as a pale yellow solid in 84% yield (3.70 g): MS (ES+) m/z 245.9 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. custompartitioned between ethyl acetate (150 mL) and water (10 mL)
  4. washThe organic phase was washed with water (2 10 mL) and brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated in diethyl ether (20 mL)
  9. washwashed with hexanes (20 mL)
  10. custompurified by column chromatography
  11. washeluting with a 0-100% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-92110ec3f8444305bc45712eed9de0f7
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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