Methyl iodide → HCID 66601526, compound

HRID 336957Notes

Reaction equation

HRID 336957 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]([CH2:32][CH3:33])(=[O:31])=[O:30])[CH:4]=1)#[N:2].[CH3:34][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[CH3:34])=[C:5]([S:29]([CH2:32][CH3:33])(=[O:31])=[O:30])[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 66601686HCID 66601686, compound

Product 1

HCID 66601526HCID 66601526, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The reaction was carried out under argon. (4S)-4-[4-Cyano-2-(ethylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (71.2 mg, 0.15 mmol) was initially charged in absolute THF (6 ml), and a 1 M solution of lithium hexamethyldisilazide (LiHMDS) in THF (180 μl; 1.2 eq.) was added at −78° C. After 20 min of stirring, iodomethane (47 μl; 5 eq.) was added, and the mixture was stirred with gradual warming from −78° C. to RT for 60 h. The reaction mixture was then purified directly 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 (60 mg, 82% of theory).

Workup

  1. stirringthe mixture was stirred
  2. temperaturewith gradual warming from −78° C. to RT for 60 h
  3. customThe reaction mixture was then purified directly by preparative HPLC (column

Sources & evidence

ORD record
ord-b8839d38e96c47189dd0c6b795ad793c
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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