Methyl iodide → 3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 2241232Notes

Reaction equation

HRID 2241232 reaction equation
[C:1]1([NH:7][C:8]2[NH:13][C:12](=[O:14])[CH:11]=[CH:10][N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Li+].I[CH3:18]>CN(C=O)C>[CH3:18][N:13]1[C:12](=[O:14])[CH:11]=[CH:10][N:9]=[C:8]1[NH:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 62714Lithium hydrideHCID 14038522-Anilino-4-hydroxypyrimidine

Product 1

HCID 685179403-methyl-2-(phenylamino)pyrimidin-4(3H)-oneYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(phenylamino)pyrimidin-4(3H)-one (0.250 g, 1.34 mmol) in DMF (10 mL) was added LiH (0.012 g, 1.47 mmol). The reaction mixture was stirred for 25 minutes and then iodomethane (0.166 mL, 2.67 mmol) was added. The reaction was stirred at room temperature for 18 hours, the quenched with H2O and partitioned between EtOAc and saturated aqueous NaCl. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude yellow oil. The crude product was purified by flash column chromatography, eluting with 30:1 dichloromethane/methanol. The desired product (0.166 g, 62%) was obtained as a white crystalline solid. 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J=6.2 Hz, 1H), 7.46 (m, 2H), 7.39 (t, J=7.8 Hz, 2H), 7.19 (t, J=7.4 Hz, 1H), 6.48 (s, 1H), 6.01 (d, J=6.6 Hz, 1H), 3.58 (s, 3H). LRMS (ESI pos) m/e 202 (M+1).

Workup

  1. stirringThe reaction was stirred at room temperature for 18 hours
  2. customthe quenched with H2O
  3. custompartitioned between EtOAc and saturated aqueous NaCl
  4. customThe phases were separated
  5. extractionthe aqueous phase was re-extracted with EtOAc (1×)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a crude yellow oil
  10. customThe crude product was purified by flash column chromatography
  11. washeluting with 30:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-0611399546a7499c9b8be79ad3059a16
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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