Methyl iodide → HCID 58133380, compound

HRID 1042316Notes

Reaction equation

HRID 1042316 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[NH:10][C:11](=[O:24])[CH2:12][C:13]1[C:18]([CH2:19][CH3:20])=[CH:17][C:16]([CH3:21])=[CH:15][C:14]=1[CH2:22][CH3:23].I[CH3:27].[H-].[Na+]>CN(C)C=O>[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[N:10]([C:11](=[O:24])[CH2:12][C:13]1[C:18]([CH2:19][CH3:20])=[CH:17][C:16]([CH3:21])=[CH:15][C:14]=1[CH2:22][CH3:23])[CH3:27]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58133384HCID 58133384, compound

Product 1

HCID 58133380HCID 58133380, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[2-(2,6-diethyl-4-methyl-phenyl)-acetylamino]-nicotinic acid methyl ester (Example 1.2) (460 mg) in N,N-dimethylformamide (5 ml) was added iodomethane (0.42 ml) at between −5° C. and 0° C. under a nitrogen atmosphere. The reaction mixture was stirred for 2 minutes before the addition of sodium hydride (60 mg) (60% by weight dispersion in mineral oil) in one portion at between −5° C. and 0° C. The reaction mixture was stirred at between −5° C. and 0° C. for 1 hour, and then at ambient temperature for 2 hours. The reaction mixture was partitioned between diethylether and aqueous hydrochloric acid (2M). The phases were separated and the organic phase was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: 10% ethyl acetate/dichloromethane) to give 2-{[2-(2,6-diethyl-4-methyl-phenyl)-acetyl]-methyl-amino}-nicotinic acid methyl ester as a light orange oil (370 mg). 1H-NMR (400 MHz, CDCl3): 8.76 (m, 1H), 8.36-8.38 (m, 1H), 7.44-7.47 (m, 1H), 6.83 (s, 2H), 3.97 (s, 3H), 3.33 (bs, 2H), 3.27 (bs, 3H), 2.47-2.57 (m, 4H), 2.26 (bs, 3H), 1.09-1.12 (m, 6H) ppm.

Workup

  1. waitat ambient temperature for 2 hours
  2. customThe reaction mixture was partitioned between diethylether and aqueous hydrochloric acid (2M)
  3. customThe phases were separated
  4. washthe organic phase was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (eluent: 10% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-07cbbc2dc1154ec6adbbe1d2cabd3b5a
Source dataset
uspto-grants-2013_10
Patent number
US08557840B2

Reaction notes

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