Potassium Iodide → (4S)-4-[2-(Benzylsulfonyl)-4-cyanophenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

HRID 2064414Notes

Reaction equation

HRID 2064414 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C@@H:12]2[C:17]([C:18]#[N:19])=[C:16]([CH3:20])[N:15]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:14](=[O:31])[N:13]2[CH3:32])=[C:7]([S:9]([O-:11])=[O:10])[CH:8]=1)#[N:2].[Na+].[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[I-].[K+]>CN(C=O)C>[CH2:34]([S:9]([C:7]1[CH:8]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=1[C@@H:12]1[C:17]([C:18]#[N:19])=[C:16]([CH3:20])[N:15]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:29])([F:30])[F:28])[CH:22]=2)[C:14](=[O:31])[N:13]1[CH3:32])(=[O:11])=[O:10])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 7498Benzyl Bromide2×HCID 66924241Sodium 5-cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfinate

Product 1

HCID 66612806(4S)-4-[2-(Benzylsulfonyl)-4-cyanophenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

The reaction was carried out under argon. Sodium 5-cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfinate (150 mg, 101 μmol; purity 32%) was suspended in DMF (1 ml). Benzyl bromide (173 mg, 1.01 mmol; 10 eq.) was then added, and the mixture was heated in a closed tube at 110° C. for 24 h. Molecular sieve (4 Å), potassium iodide (110 mg, 0.66 mmol) and further benzyl bromide (173 mg, 1.01 mmol; 10 eq.) were then added, and the reaction mixture was again heated in a closed tube at 100° C. for 6 h. The mixture was then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). The title compound was obtained as a solid (49.3 mg, 89% of theory).

Workup

  1. temperaturethe reaction mixture was again heated in a closed tube at 100° C. for 6 h
  2. filtrationThe mixture was then filtered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)

Sources & evidence

ORD record
ord-952327f64ea043fab0c6fd8ddaf03183
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

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