Sodium hydride → 3-bromo-4-[(2,4-difluorobenzyl)oxy]-1-({5-[(2-methoxyethoxy)methyl]pyrazin-2-yl}methyl)-6-methylpyridin-2(1H)-one

HRID 1867012Notes

Reaction equation

HRID 1867012 reaction equation
[Br:1][C:2]1[C:3](=[O:28])[N:4]([CH2:19][C:20]2[CH:25]=[N:24][C:23]([CH2:26][OH:27])=[CH:22][N:21]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[H-].[Na+].[CH3:31][O:32][CH2:33][CH2:34]Br>CC(N(C)C)=O>[Br:1][C:2]1[C:3](=[O:28])[N:4]([CH2:19][C:20]2[CH:25]=[N:24][C:23]([CH2:26][O:27][CH2:34][CH2:33][O:32][CH3:31])=[CH:22][N:21]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 220506073-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-{[5-(hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(1H)-one

Product 1

HCID 220504893-bromo-4-[(2,4-difluorobenzyl)oxy]-1-({5-[(2-methoxyethoxy)methyl]pyrazin-2-yl}methyl)-6-methylpyridin-2(1H)-oneYield 80%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-{[5-(hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(1H)-one (0.25 g, 0.00055 mol) in dimethyl acetamide at 0° C., was added NaH (0.016 g, 0.00067 mol) and stirred for 15 min. 2-Methoxyethyl bromide (0.09 g, 0.00-65 mol) was then added, and the mixture was stirred at room temperature for 6 h. Dimethylacetamide was distilled in vacuo and the product was purified by reverse-phase HPLC using 10-90% acetonitrile/water gradient (30 min) at a flow rate of 100 mL/min. The appropriate fractions (m/z=510) were combined and freeze dried to afford the title compound (0.32 g, 80%) as a white powder:

Workup

  1. stirringthe mixture was stirred at room temperature for 6 h
  2. distillationDimethylacetamide was distilled in vacuo
  3. customthe product was purified by reverse-phase
  4. custom10-90% acetonitrile/water gradient (30 min)
  5. customfreeze dried

Sources & evidence

ORD record
ord-71b0bced5cde4c64a2988d888345bd0c
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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