Acetylacetone → 4-{5-Acetyl-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-4-pyrimidinyl}benzonitrile

HRID 1921123Notes

Reaction equation

HRID 1921123 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].[CH3:25][C:26](=O)[CH2:27][C:28](=[O:30])[CH3:29]>C1COCC1>[C:28]([C:27]1[CH:21]([C:20]2[CH:23]=[CH:24][C:17]([C:15]#[N:16])=[CH:18][CH:19]=2)[NH:12][C:10](=[S:11])[N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:13])[F:14])[CH:4]=2)[C:26]=1[CH3:25])(=[O:30])[CH3:29]

Participants

5

Reactant 3

HCID 31261AcetylacetoneHCID 660424-CyanobenzaldehydeHCID 7358443-(Trifluoromethyl)phenylthiourea

Product 1

HCID 115968194-{5-Acetyl-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-4-pyrimidinyl}benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Trifluoromethylphenyl thiourea (200 mg, 0.91 mmol), 4-cyanobenzaldehyde (238.2 mg, 1.82 mmol) and 2,4-pentanedione (181.9 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-40412c4a333b4447b0013a4350d650c3
Source dataset
uspto-grants-2012_05
Patent number
US08173665B2

Reaction notes

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