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

HRID 230274

Reaction equation

HRID 230274 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][CH3:32])(=[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][CH3:32])=[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 7757Methyl acetoacetateHCID 660424-CyanobenzaldehydeHCID 7358443-(Trifluoromethyl)phenylthiourea

Product 1

HCID 57762471Methyl 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 (200 mg, 0.91 mmol), 4-cyanobenzaldehyde (238.2 mg, 1.82 mmol) and methyl acetoacetate (211 mg, 1.82 mmol) are dissolved in 5 ml THF. Ethyl polyphosphate (0.30 g) is added and the reaction mixture is stirred at reflux temperature overnight. After cooling to room temperature, the reaction is quenched with 10 ml of water and extracted with 10 ml ethyl 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. customthe reaction is quenched with 10 ml of water
  3. extractionextracted with 10 ml ethyl 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-423d44f2d1b94d9b8d882b391c16cd6f
Source dataset
uspto-grants-2009_07
Patent number
US07566723B2

Linked notes

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