(Trifluoromethyl)trimethylsilane → (4S)-4-{4-Cyano-2-[(trifluoromethyl)sulfonyl]phenyl}-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

HRID 707620Notes

Reaction equation

HRID 707620 reaction equation
[F:1][C:2]([Si](C)(C)C)([F:4])[F:3].[C:9]([C:11]1[CH:12]=[CH:13][C:14]([C@@H:21]2[C:26]([C:27]#[N:28])=[C:25]([CH3:29])[N:24]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=3)[C:23](=[O:40])[N:22]2[CH3:41])=[C:15]([S:17](Cl)(=[O:19])=[O:18])[CH:16]=1)#[N:10]>C1COCC1>[C:9]([C:11]1[CH:12]=[CH:13][C:14]([C@@H:21]2[C:26]([C:27]#[N:28])=[C:25]([CH3:29])[N:24]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=3)[C:23](=[O:40])[N:22]2[CH3:41])=[C:15]([S:17]([C:2]([F:4])([F:3])[F:1])(=[O:19])=[O:18])[CH:16]=1)#[N:10]

Participants

4

Reactant 2

HCID 552549(Trifluoromethyl)trimethylsilane2×HCID 866507215-Cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfonyl chloride

Product 1

HCID 86650727(4S)-4-{4-Cyano-2-[(trifluoromethyl)sulfonyl]phenyl}-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The reaction was carried out under argon. Tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF; 18.4 mg, 66.7 μmol; 1.1 eq.) and (trifluoromethyl)trimethylsilane (2 M solution in THF, 60.6 μl, 121 μmol) were initially charged in THF (1.45 ml) at 0° C. 5-Cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfonyl chloride (30 mg, 60.6 μmol) was added, and the mixture was stirred at RT overnight. More tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF; 16.7 mg, 60.6 μmol; 1.0 eq.) and (trifluoromethyl)trimethylsilane (2 M solution in THF, 65 μl, 130 μmol) were then added at 0° C., and the mixture was again stirred for 15 h with gradual warming to RT. 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 (3.3 mg, 10% of theory).

Workup

  1. stirringthe mixture was again stirred for 15 h
  2. temperaturewith gradual warming to RT
  3. filtrationThe mixture was then filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. 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-3d5b3a0943ff448bbb49910cd431553d
Source dataset
uspto-grants-2015_11
Patent number
US09174997B2

Reaction notes

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