Sodium hydride → HCID 67477363, compound

HRID 2361919Notes

Reaction equation

HRID 2361919 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:11](=[O:28])[NH:10]2)=[C:5]([S:29]([CH3:31])=[O:30])[CH:4]=1)#[N:2].C(C1C=CC([C@@H]2C(C#N)=C(C)N(C3C=CC=C(C(F)(F)F)C=3)C(=O)N2)=C([S@](C)=O)C=1)#N.[H-].[Na+].[CH3:65][S:66](Cl)(=[O:68])=[O:67].[Cl-].[NH4+]>C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:11](=[O:28])[N:10]2[S:66]([CH3:65])(=[O:68])=[O:67])=[C:5]([S@:29]([CH3:31])=[O:30])[CH:4]=1)#[N:2]

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chloride2×HCID 66601649HCID 66601649, compoundHCID 66601650HCID 66601650, compound

Product 1

HCID 67477363HCID 67477363, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The reaction was carried out under argon. The diastereomer mixture of (RS,4S)-4-[4-cyano-2-(methylsulfinyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile and (SS,4S)-4-[4-cyano-2-(methylsulfinyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (444.4 mg, 1000 μmol) was initially charged in THF (10 ml), and sodium hydride (60% in mineral oil; 56 mg, 1400 μmol) was added at 0° C. The mixture was warmed to RT and stirred for 20 min. A solution of methanesulfonyl chloride (160.4 mg, 1400 μmol; 1.4 eq.) in THF (5 ml) was then slowly added dropwise. After a reaction time of 16 h, more methanesulfonyl chloride (54 mg, 467 μmol; 0.47 eq.) was added and the mixture was stirred at RT for another 60 min. Saturated ammonium chloride solution (50 ml) was added, and the reaction mixture then extracted with ethyl acetate (3×30 ml). The combined organic phases were dried over solid sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20). This gave the title compound as a colorless solid (245 mg, 47% of theory).

Workup

  1. stirringthe mixture was stirred at RT for another 60 min
  2. extractionthe reaction mixture then extracted with ethyl acetate (3×30 ml)
  3. dry with materialThe combined organic phases were dried over solid sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20)

Sources & evidence

ORD record
ord-9e1d43b710074616b323ce693bf3cdc8
Source dataset
uspto-grants-2014_04
Patent number
US08691817B2

Reaction notes

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