Ethyl Acetoacetate → Ethyl 4-(4-cyanophenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

HRID 1921125Notes

Reaction equation

HRID 1921125 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([NH2:12])=[S:11])[CH:6]=[CH:7][CH:8]=1.[C:15]([C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1)#[N:16].[C:25]([O:31][CH2:32][CH3:33])(=[O:30])[CH2:26][C:27]([CH3:29])=O>C1COCC1>[C:15]([C:17]1[CH:24]=[CH:23][C:20]([CH:21]2[C:26]([C:25]([O:31][CH2:32][CH3:33])=[O:30])=[C:27]([CH3:29])[N:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:13])[F:14])[CH:4]=3)[C:10](=[S:11])[NH:12]2)=[CH:19][CH:18]=1)#[N:16]

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 660424-CyanobenzaldehydeHCID 7358443-(Trifluoromethyl)phenylthiourea

Product 1

HCID 57762441Ethyl 4-(4-cyanophenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Trifluoromethylphenyl thiourea (3.00 g, 13.6 mmol), 4-cyanobenzaldehyde (3.57 g, 27.3 mmol) and ethyl acetoacetate (3.55 g, 27.3 mmol) are dissolved in 50 ml THF. Ethyl polyphosphate (4.50 g) is added and the reaction mixture is stirred at reflux temperature overnight. After cooling to room temperature, it is quenched with 50 ml of water and extracted with 100 methyl acetate (2×). The combined organic layers are dried with sodium sulfate and the solvent is removed in vacuo. The product is purified via preparative HPLC (RP18-column; eluent: acetonitrile-water, gradient 10:90 to 90:10).

Workup

  1. temperatureat reflux temperature overnight
  2. customit is quenched with 50 ml of water
  3. extractionextracted with 100 methyl acetate (2×)
  4. dry with materialThe combined organic layers are dried with sodium sulfate
  5. customthe solvent is removed in vacuo
  6. customThe product is purified via preparative HPLC (RP18-column; eluent: acetonitrile-water, gradient 10:90 to 90:10)

Sources & evidence

ORD record
ord-d9a21b98eac74f68b569f714c64847c8
Source dataset
uspto-grants-2012_05
Patent number
US08173665B2

Reaction notes

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