Morpholine → (rac)-4-[4-Cyano-2-(methylsulfanyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

HRID 2361915Notes

Reaction equation

HRID 2361915 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([O:17]CC=C)=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([S:33][CH3:34])[CH:4]=1)#[N:2].N1CCOCC1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([OH:17])=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:30])([F:29])[F:31])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([S:33][CH3:34])[CH:4]=1)#[N:2]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 44133410Allyl(rac)-4-[4-cyano-2-(methylsulfanyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Product 1

HCID 58133753(rac)-4-[4-Cyano-2-(methylsulfanyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

Allyl (rac)-4-[4-cyano-2-(methylsulfanyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (750 mg, 1.54 mmol) was dissolved in THF (10 ml), and morpholine (201 mg, 2.308 mmol) was added. The reaction solution was saturated with argon (argon was passed through the solution for 30 min). Tetrakis(triphenylphosphine)palladium(0) (7.47 mg, 0.006 mmol) was then added, and the mixture was stirred at RT overnight. Since HPLC showed little conversion, more tetrakis(triphenylphosphine)palladium(0) (7.47 mg, 0.006 mmol) was added and the mixture was stirred at RT for a further 3 h. The content of the flask was then filtered through kieselguhr and the residue was washed with THF. The filtrate was concentrated under reduced pressure and the residue was recrystallized from diethyl ether (15 ml). The crystals were filtered off with suction and dried under high vacuum. This gave 663 mg (96% of theory) of the target compound.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at RT for a further 3 h
  3. filtrationThe content of the flask was then filtered through kieselguhr
  4. washthe residue was washed with THF
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was recrystallized from diethyl ether (15 ml)
  7. filtrationThe crystals were filtered off with suction
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-cd6925a96670404e945bbad62869682b
Source dataset
uspto-grants-2014_04
Patent number
US08691817B2

Reaction notes

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