1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-(4-Cyanophenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

HRID 230282Notes

Reaction equation

HRID 230282 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([O:17]CCC#N)=[O:16])=[C:13]([CH3:22])[N:12]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)[C:11](=[S:33])[NH:10]2)=[CH:5][CH:4]=1)#[N:2].N12CCCN=C1CCCCC2>O1CCOCC1.Cl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[C:14]([C:15]([OH:17])=[O:16])=[C:13]([CH3:22])[N:12]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)[C:11](=[S:33])[NH:10]2)=[CH:7][CH:8]=1)#[N:2]

Participants

5

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 866051352-Cyanoethyl 4-(4-cyanophenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

Product 1

HCID 577624474-(4-Cyanophenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Cyanoethyl 4-(4-cyanophenyl)-6-methyl-2-thioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate (Example 16; 47 mg, 0.1 mmol) is dissolved in 0.5 ml dioxane. After addition of 1,8-diazabicyclo[5.4.0]undec-7-ene (15 μl, 15 mg, 0.1 mmol), the reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is diluted with 1 N hydrochloric acid and extracted with ethyl acetate. After drying with magnesium sulfate and evaporating off the solvent, the residue is purified by preparative HPLC (column: Nucleosil 100-5 C 18 Nautilus 20 mm×50 mm, 5 μm; solvent A: acetonitrile, solvent B: water+0.1% formic acid; flow rate: 25 ml/min; gradient: 0 min 10% A, 2 min 10% A, 6 min 90% A, 7 min 90% A, 7.1 min 10% A, 8 min 10% A; wavelength: 220 nm; injection volume: approx. 550 μl; number of injections: 1). The product containing fractions are combined and concentrated in vacuo.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialAfter drying with magnesium sulfate
  3. customevaporating off the solvent
  4. customthe residue is purified by preparative HPLC (column: Nucleosil 100-5 C 18 Nautilus 20 mm×50 mm, 5 μm; solvent A: acetonitrile, solvent B: water+0.1% formic acid; flow rate: 25 ml/min; gradient: 0 min 10% A, 2 min 10% A, 6 min 90% A, 7 min 90% A, 7.1 min 10% A, 8 min 10% A; wavelength: 220 nm; injection volume: approx. 550 μl; number of injections: 1)
  5. additionThe product containing fractions
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b1d61a3c6f8c467faa0ef08731d3544b
Source dataset
uspto-grants-2009_07
Patent number
US07566723B2

Reaction notes

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