(3-Trifluoromethylphenyl)urea → 4-[5-Acetyl-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-3-bromo-benzonitrile

HRID 926999Notes

Reaction equation

HRID 926999 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH:10]=O)[C:5]#[N:6].[C:12]([CH2:15][C:16](=[O:18])[CH3:17])(=O)[CH3:13].[F:19][C:20]([F:32])([F:31])[C:21]1[CH:22]=[C:23]([NH:27][C:28]([NH2:30])=[O:29])[CH:24]=[CH:25][CH:26]=1>O1CCCC1>[C:16]([C:15]1[CH:10]([C:9]2[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=2[Br:1])[NH:30][C:28](=[O:29])[N:27]([C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([C:20]([F:31])([F:32])[F:19])[CH:22]=2)[C:12]=1[CH3:13])(=[O:18])[CH3:17]

Participants

5

Reactant 3

HCID 25712(3-Trifluoromethylphenyl)ureaHCID 31261AcetylacetoneHCID 205105183-Bromo-4-formylbenzonitrile2×

Product 1

HCID 1186916954-[5-Acetyl-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-3-bromo-benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Bromo-4-formyl-benzonitrile (intermediate 2, 1.09 g, 4.92 mmol) is stirred with acetylacetone (0.60 mL, 5.88 mmol), 3-(trifluoromethyl)phenylurea (1.00 g, 4.90 mmol) and polyphosphoric acid (3.02 g, 7.90 mmol) in tetrahydrofurane (40.0 mL) at 50° C. overnight. The reaction mixture is concentrated in vacuo, ethyl acetate and water is added and the phases are separated. The aqueous phase is extracted twice with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over MgSO4 and concentrated. Yield: 2.38 g; ESI mass spectrum: [(79Br)-M+H]+=478, [(81Br)-M+H]+=480; Retention time HPLC: 1.06 min (HPLC method Z018_S04).

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo, ethyl acetate and water
  2. additionis added
  3. customthe phases are separated
  4. extractionThe aqueous phase is extracted twice with ethyl acetate
  5. washThe combined organic phases are washed with saturated sodium chloride solution
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. custom1.06 min (HPLC method Z018_S04)

Sources & evidence

ORD record
ord-dc56eff630b4457aaecc9f3201932ea0
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

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