Sodium Iodide → 1-methyl-5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2(1H)-one

HRID 2207363Notes

Reaction equation

HRID 2207363 reaction equation
I[CH3:2].[I-].[Na+].C[O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]([NH:19][C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=3)[CH:16]=[CH:17][CH:18]=2)=[CH:9][CH:8]=1>CC#N>[CH3:2][N:12]1[CH:11]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:20]3[N:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][N:21]=3)[CH:14]=2)[CH:9]=[CH:8][C:7]1=[O:6]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 6328Methyl iodideHCID 131735890N-[3-(6-methoxypyridin-3-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 1180926351-methyl-5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

Iodomethane (0.063 mL, 1.007 mmol) and sodium iodide (151 mg, 1.007 mmol) were added to a solution of N-[3-(6-methoxypyridin-3-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (109 mg, 0.315 mmol) in MeCN (3.1 mL) at room temperature under nitrogen. The mixture was heated to 45° C. for 72 hours, then cooled to room temperature and concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford 1-methyl-5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2(1H)-one as an off-white solid. MS APC calc'd for C17H14F3N4O [M+H]+ 347. found 347. Check LCMS data. 1H NMR (400 MHz, Acetone-d6): δ 9.31 (s, 1H); 8.83 (d, J=4.9 Hz, 1H); 8.72 (s, 1H); 7.96 (d, J=8.2 Hz, 1H); 7.84 (d, J=7.8 Hz, 1H); 7.79 (t, J=7.8 Hz, 1H); 7.54 (d, J=7.4 Hz, 1H); 7.48 (t, J=7.9 Hz, 1H); 7.24 (d, J=4.9 Hz, 1H); 6.76 (d, J=8.2 Hz, 1H); 4.04 (s, 3H). APCI: [M+H]+ m/z 347.1.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with water
  4. extractionextracted with ethyl acetate (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-69bf6e40961f48b8a22d04455c085f8f
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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