Sodium hydride → HCID 66612257, compound

HRID 336971Notes

Reaction equation

HRID 336971 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].[H-].[Na+].[CH3:34][S:35](Cl)(=[O:37])=[O:36].[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:35]([CH3:34])(=[O:37])=[O:36])=[C:5]([S:29]([CH3:31])=[O:30])[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 66601649HCID 66601649, compound

Product 1

HCID 66612257HCID 66612257, compoundYield 40.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The reaction was carried out under argon. (4S)-4-{4-Cyano-2-[methylsulfinyl]phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (444 mg, 1 mmol) was initially charged in dry THF (10 ml), and sodium hydride (60% in mineral oil; 56 mg, 1.4 mmol; 1.4 eq.) was added at 0° C. The mixture was warmed to RT and stirred for 20 min. A solution of methanesulfonyl chloride (160 mg, 1.4 mmol; 1.4 eq.) in THF (5 ml) was then slowly added dropwise. After a reaction time of 16 h, ammonium chloride solution (50 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (3×30 ml). The combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20). This gave the title compound as a solid (210 mg, 40% of theory).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×30 ml)
  2. dry with materialThe combined organic phases were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→80:20)

Sources & evidence

ORD record
ord-de9883ec9cb64d2482eb5e400350bb7e
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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