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

HRID 1921137Notes

Reaction equation

HRID 1921137 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: acetonitrile-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: acetonitrile-water, gradient 10:90 to 90:10)

Sources & evidence

ORD record
ord-cff2f737952e4f49a0f9655b2e7db2c7
Source dataset
uspto-grants-2012_05
Patent number
US08173665B2

Reaction notes

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