Methyl iodide → HCID 67477445, compound

HRID 2361918Notes

Reaction equation

HRID 2361918 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:32](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.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].IC>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[CH3:32])=[C:5]([S@:29]([CH3:31])=[O:30])[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 66601649HCID 66601649, compoundHCID 66601650HCID 66601650, compound

Product 1

HCID 67477445HCID 67477445, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

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 (535 mg, 1.2 mmol) was initially charged in absolute THF (12 ml), and a 1 M solution of lithium hexamethyldisilazide (LiHMDS) in THF (1.45 ml; 1.2 eq.) was added at −78° C. After 20 min of stirring at −78° C., iodomethane (854 mg; 5 eq.) was added and the mixture was stirred for 16 h with gradual warming from −78° C. to RT. The reaction mixture was then concentrated under reduced pressure, saturated ammonium chloride solution (50 ml) was added and the mixture was then extracted with ethyl acetate (3×30 ml). The combined organic phases were dried over solid sodium sulfate, filtered and concentrated under reduced pressure and the residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave the title compound as a solid (488 mg, 88% of theory).

Workup

  1. stirringthe mixture was stirred for 16 h
  2. temperaturewith gradual warming from −78° C. to RT
  3. concentrationThe reaction mixture was then concentrated under reduced pressure, saturated ammonium chloride solution (50 ml)
  4. additionwas added
  5. extractionthe mixture was then extracted with ethyl acetate (3×30 ml)
  6. dry with materialThe combined organic phases were dried over solid sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. 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-f90324e17f8445b189b6f7377a8a08d2
Source dataset
uspto-grants-2014_04
Patent number
US08691817B2

Reaction notes

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