Hydrochloric Acid → Ethyl 4-(4-cyano-2-methylphenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

HRID 230284

Reaction equation

HRID 230284 reaction equation
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[C:5]([CH3:11])[CH:4]=1)#[N:2].[F:12][C:13]([F:25])([F:24])[C:14]1[CH:15]=[C:16]([NH:20][C:21]([NH2:23])=[S:22])[CH:17]=[CH:18][CH:19]=1.O=[C:27]([CH3:34])[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30].C[Si](OP(=O)=O)(C)C.Cl>C1COCC1>[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]2[C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[C:27]([CH3:34])[N:20]([C:16]3[CH:17]=[CH:18][CH:19]=[C:14]([C:13]([F:12])([F:24])[F:25])[CH:15]=3)[C:21](=[S:22])[NH:23]2)=[C:5]([CH3:11])[CH:4]=1)#[N:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8868Ethyl AcetoacetateHCID 7358443-(Trifluoromethyl)phenylthioureaHCID 109096954-Formyl-3-methylbenzonitrileHCID 16133246Trimethyl(phosphooxy)silane

Product 1

HCID 57762430Ethyl 4-(4-cyano-2-methylphenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Cyano-2-methylbenzaldehyde (200 mg, 1.38 mmol), 3-trifluoromethylphenyl thiourea (276 mg, 1.25 mmol), ethyl 3-oxobutanoate (179 mg, 1.38 mmol) and trimethylsilyl polyphosphate (225 mg) in 5 ml THF are stirred overnight at reflux temperature. The reaction mixture is cooled to room temperature, and after addition of 20 ml 0.5 M hydrochloric acid the aqueous phase is extracted with ethyl acetate (2×20 ml). The combined organic layers are washed with saturated aqueous sodium carbonate solution and dried with sodium sulfate. The solvent is removed in vacuo and the crude product is purified via preparative HPLC (RP18-column; eluent: aceto-nitrile-water, gradient 10:90 to 90:10).

Workup

  1. temperatureat reflux temperature
  2. extractionis extracted with ethyl acetate (2×20 ml)
  3. washThe combined organic layers are washed with saturated aqueous sodium carbonate solution
  4. dry with materialdried with sodium sulfate
  5. customThe solvent is removed in vacuo
  6. customthe crude product is purified via preparative HPLC (RP18-column; eluent: aceto-nitrile-water, gradient 10:90 to 90:10)

Sources & evidence

ORD record
ord-509619a7c4b04077b6a0c0fc2300104a
Source dataset
uspto-grants-2009_07
Patent number
US07566723B2

Linked notes

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