Methyl iodide → HCID 69271935, compound

HRID 218491Notes

Reaction equation

HRID 218491 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]3[C:22]([C:23]#[N:24])=[C:21]([CH3:25])[NH:20][C:19]([CH3:26])=[C:18]3[C:27]#[N:28])=[CH:14][CH:15]=2)[C:10]([CH3:29])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:32]I>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]3[C:22]([C:23]#[N:24])=[C:21]([CH3:25])[N:20]([CH3:32])[C:19]([CH3:26])=[C:18]3[C:27]#[N:28])=[CH:14][CH:15]=2)[C:10]([CH3:29])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69267720HCID 69267720, compound

Product 1

HCID 69271935HCID 69271935, compoundYield 82.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

12.36 g (3173 mmol) 5-(3,5-dicyano-2,6-dimethyl-1,4-dihydro-pyridin-4-yl)-3-methyl-indazole-1-carboxylic acid tert-butyl ester, from Synthetic Example 15, were dissolved in 158 mL N,N-dimethylformamide. 1.62 g (40.61 mmol) sodium hydride (as a dispersion in mineral oil) were added and the mixture stirred for 20 minutes. 2.37 mL (38.08 mmol) methyl iodide were added and the mixture stirred for 2.5 hours. The solvent was distilled off under vacuum and the residue was taken up in ethyl acetate, washed with water and saturated sodium chloride solution and dried over sodium sulfate. Purification with column chromatography afforded 5-(3,5-dicyano-1,2,6-trimethyl-1,4-dihydro-pyridin-4-yl)-3-methyl-indazole-1-carboxylic acid tert-butyl ester (10.56 g, 82.5%). 1H-NMR (DMSO-D6): δ=8.06 (d, 1H), 7.67 (s, 1H), 7.56 (d, 1H), 4.56 (s, 1H), 3.22 (s, 3H), 2.54 (s, 3H), 2.25 (s, 6H), 1.64 (s, 9H) ppm. MS (ES+): 404.45 (M++1, 75%).

Workup

  1. stirringthe mixture stirred for 2.5 hours
  2. distillationThe solvent was distilled off under vacuum
  3. washwashed with water and saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. customPurification with column chromatography

Sources & evidence

ORD record
ord-b91a6a312e28494fa58dcae400d3e743
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Reaction notes

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