Methyl iodide → HCID 24826274, compound

HRID 230691Notes

Reaction equation

HRID 230691 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][NH:19][C:20](=[O:23])[CH:21]=[CH2:22])=[CH:14][CH:13]=2)[N:4]=1.[H-].[Na+].[CH3:28]I>CN(C)C=O>[CH3:28][N:19]([CH2:18][C:15]1[CH:16]=[CH:17][C:12]([N:5]2[C:6]3[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=3[C:3]([C:2]([F:1])([F:24])[F:25])=[N:4]2)=[CH:13][CH:14]=1)[C:20](=[O:23])[CH:21]=[CH2:22]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 24826184HCID 24826184, compound

Product 1

HCID 24826274HCID 24826274, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of N-({4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]phenyl}methyl)-2-propenamide (241 mg, 0.69 mmol) in dimethylformamide (5 ml) under argon was treated with sodium hydride (60% suspension in mineral oil, 28 mg, 0.7 mmol). The reaction mixture was stirred for 5 minutes then methyl iodide (0.05 ml) was added and the reaction mixture stirred for a further 1 hour. Reaction mixture was then quenched with 3 drops of water and 5 ml of 1M ammonia in methanol. Excess ammonia and methanol were removed by rotary evaporation. Reaction mixture was separated between ethyl acetate and brine. Organic layer was retained, dried over sodium sulphate and the solvent removed by rotary evaporation. Sample was purified by 5 g pre-pack silica column eluted with 50% ethyl acetate/petroleum ether. Relevant fractions were combined and the solvent removed by rotary evaporation to give the title compound as a yellow oil (66 mg, 26%).

Workup

  1. stirringthe reaction mixture stirred for a further 1 hour
  2. customReaction mixture
  3. customwas then quenched with 3 drops of water and 5 ml of 1M ammonia in methanol
  4. customExcess ammonia and methanol were removed by rotary evaporation
  5. customReaction mixture
  6. customwas separated between ethyl acetate and brine
  7. dry with materialdried over sodium sulphate
  8. customthe solvent removed by rotary evaporation
  9. customSample was purified by 5 g pre-pack silica column
  10. washeluted with 50% ethyl acetate/petroleum ether
  11. customthe solvent removed by rotary evaporation

Sources & evidence

ORD record
ord-bb604c55925f495bb4e9e012cf77dbf5
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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