Methyl iodide → 6-Chloro-1-methyl-1H-indole-2-carboxylic acid [2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide

HRID 1883129Notes

Reaction equation

HRID 1883129 reaction equation
[C:1]([CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[NH:13][C:14]([C:16]1[NH:17][C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[C:20]([Cl:25])[CH:19]=2)=[O:15])=[O:6])#[N:2].[H-].[Na+].[CH3:28]I>CN(C=O)C>[C:1]([CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[NH:13][C:14]([C:16]1[N:17]([CH3:28])[C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[C:20]([Cl:25])[CH:19]=2)=[O:15])=[O:6])#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 235102346-Chloro-1h-indole-2-carboxylic acid[2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide

Product 1

HCID 207403236-Chloro-1-methyl-1H-indole-2-carboxylic acid [2-(cyanomethyl-carbamoyl)-cyclohexyl]-amideYield 74.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-Chloro-1H-indole-2-carboxylic acid [2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide (6.17 g, 17.19 mmol) in DMF (35 ml) were added NaH as a 60% wt suspension in mineral oil (0.687 g, 17.19 mmol) at 0° C. The slurry was stirred for one hour at room temperature and methyl iodide (1.07 ml, 17.19 mmol) was added. The solution was stirred for four hours and partitioned between ethyl acetate (200 ml) and 1 N HCl (300 ml). The organic layer was washed with water, brine, dried over magnesium sulfate and concentrated. Recrystallizing from ethyl acetate: hexane (1:10) yielded 6-Chloro-1-methyl-1H-indole-2-carboxylic acid [2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide (4.76 g, 74%). [M+H=373].

Workup

  1. stirringThe solution was stirred for four hours
  2. custompartitioned between ethyl acetate (200 ml) and 1 N HCl (300 ml)
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customRecrystallizing from ethyl acetate: hexane (1:10)

Sources & evidence

ORD record
ord-457d961c91be48abb99d8202e17dfc16
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

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