Methyl iodide → HCID 18763063, compound

HRID 2186887Notes

Reaction equation

HRID 2186887 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]2[N:15]([CH3:16])[C:14]3[CH:17]=[CH:18][C:19]([NH:21][C:22](=O)C(F)(F)F)=[CH:20][C:13]=3[N:12]=2)=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].CI>CS(C)=O.C(OCC)(=O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]2[N:15]([CH3:16])[C:14]3[CH:17]=[CH:18][C:19]([NH:21][CH3:22])=[CH:20][C:13]=3[N:12]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 18762988HCID 18762988, compound

Product 1

HCID 18763063HCID 18763063, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

4.1 g (11 mmol) of N-{2-[2-(4-cyanophenyl)-ethyl]-1-methyl-benzimidazol-5-yl}-trifluoroacetamide are cooled to about 10° C. in 20 mL dimethylsulphoxide and 80% NaH (0.33 g, about 11 mmol) are added in batches with stirring. The mixture is heated to 40-50° C. for 0.5 h and then cooled to 30° C. Methyl iodide (0.75 mL, 11.9 mmol) is then added dropwise. The mixture is stirred for 0.5 h at 40-50° C., diluted with 100 mL ethyl acetate, poured onto water and extracted. The organic phase is again washed with water, dried and evaporated down. The residue is chromatographed over silica gel. The methylated trifluoroacetamide is taken up in MeOH, combined with 10 mL of conc. aqueous ammonia solution and stirred for 4 h at 30-40° C. The methanol is distilled off, the residue is taken up in 75 mL of ethyl acetate, washed with water, dried and evaporated down. The product is crystallised from diethylether. Yield: 2.0 g (63%); melting point: 155-158° C.

Workup

  1. temperaturecooled to 30° C
  2. stirringThe mixture is stirred for 0.5 h at 40-50° C.
  3. additionpoured onto water
  4. extractionextracted
  5. washThe organic phase is again washed with water
  6. customdried
  7. customevaporated down
  8. customThe residue is chromatographed over silica gel
  9. stirringstirred for 4 h at 30-40° C
  10. distillationThe methanol is distilled off
  11. washwashed with water
  12. customdried
  13. customevaporated down
  14. customThe product is crystallised from diethylether

Sources & evidence

ORD record
ord-f802921389a84a43b077ff839e5e4970
Source dataset
uspto-grants-2002_06
Patent number
US06407130B1

Reaction notes

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