Acetic Acid → HCID 46928995, compound

HRID 2361927Notes

Reaction equation

HRID 2361927 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C@@H:15]2[C:20]([C:21]#[N:22])=[C:19]([CH3:23])[N:18]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)[C:17](=[O:34])[NH:16]2)=[C:7]([S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])[CH:8]=1)#[N:2].[CH3:35][Si](C)(C)[N-][Si](C)(C)C.[Li+].IC.C(O)(=O)C>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C@@H:15]2[C:20]([C:21]#[N:22])=[C:19]([CH3:23])[N:18]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:31])[F:33])[CH:25]=3)[C:17](=[O:34])[N:16]2[CH3:35])=[C:7]([S:9]([N:12]([CH3:13])[CH3:14])(=[O:11])=[O:10])[CH:8]=1)#[N:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 46928898HCID 46928898, compound

Product 1

HCID 46928995HCID 46928995, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Under an atmosphere of argon protective gas, 5-cyano-2-{(4S)-5-cyano-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}-N,N-dimethylbenzene sulfonamide (50 mg, 108 μmol) was initially charged in absolute THF (4.5 ml), and a 1 M solution of lithium hexamethyldisilazide (LiHMDS) in THF (130 μl, 130 μmol; 1.2 eq.) was added at −78° C. After 30 min of stirring, iodomethane (77 mg, 542 μmol; 5 eq.) in THF (1 ml) was added, and the mixture was stirred for 16 h with gradual warming from −78° C. to RT. A little acetic acid was then added, and the reaction mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). This gave a colorless amorphous solid (7.6 mg, 14% 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 concentrated under reduced pressure
  4. customThe residue was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)
  5. customThis gave a colorless amorphous solid (7.6 mg, 14% of theory)

Sources & evidence

ORD record
ord-5defe3eae04e46cd930036c18dffb31d
Source dataset
uspto-grants-2014_04
Patent number
US08691817B2

Reaction notes

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