Hydrochloric Acid → 3-benzyl-5-(3-fluoro-4-methoxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

HRID 2246475Notes

Reaction equation

HRID 2246475 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=2)=[CH:11][N:10]=[C:9]1SC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1.Cl>O1CCOCC1>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=2)=[CH:11][N:10]=[C:9]1[NH:31][C:30]1[CH:32]=[CH:33][C:27]([F:26])=[CH:28][CH:29]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 97314-FluoroanilineHCID 592183693-benzyl-5-(3-fluoro-4-methoxyphenyl)-2-(methylthio)pyrimidin-4(3H)-one

Product 1

HCID 592183673-benzyl-5-(3-fluoro-4-methoxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-oneYield 71%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

3-benzyl-5-(3-fluoro-4-methoxyphenyl)-2-(methylthio)pyrimidin-4(3H)-one (697.4 mg, 1.957 mmol) was dissolved in 1,4-dioxane (10 ml) and 4-fluoroaniline (1.50 ml, 15.6 mmol) and concentrated hydrochloric acid (0.040 ml, 1.1 mmol) were added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (125 C) and stirred under nitrogen. After stirring for 70 hours, the reaction was cooled to room temperature and concentrated. It was then treated with Et2O, and filtered, and the solid was washed with Et2O and dried in vacuo to afford the desired 3-benzyl-5-(3-fluoro-4-methoxyphenyl)-2-(4-fluorophenylamino)pyrimidin-4(3H)-one (582.7 mg, 1.39 mmol, 96% purity, 67% yield over two steps). MS (ESI pos. ion) m/z: 420 (MH+). Calc'd exact mass for C24H19F2N3O2: 419. 1HNMR (400 MHz, CDCl3): 7.89 (br s, 1H), 7.53-7.37 (m, 8H), 7.13 dd, J=9.2 Hz, 4.0 Hz, 2H), 7.01 (t, J=8.0 Hz, 3H), 5.47 (s, 2H), 3.93 (s, 3H).

Workup

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. stirringAfter stirring for 70 hours
  4. concentrationconcentrated
  5. additionIt was then treated with Et2O
  6. filtrationfiltered
  7. washthe solid was washed with Et2O
  8. customdried in vacuo

Sources & evidence

ORD record
ord-f6c155fc2de34764b47a07ba33fda53c
Source dataset
uspto-grants-2010_03
Patent number
US07687522B2

Reaction notes

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