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 2064318Notes

Reaction equation

HRID 2064318 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; Example 39) was dissolved in THF (10 ml), and morpholine (201 mg, 2.308 mmol) was added. The reaction solution was saturated with argon (argon was bubbled 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, by HPLC control, only little conversion could be observed, 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 contents 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. customwas bubbled through the solution for 30 min)
  2. stirringthe mixture was stirred at RT for a further 3 h
  3. filtrationThe contents 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-444849cb5bc34227a95949602d2931e3
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

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