Sodium hydride → HCID 178490888, compound

HRID 1370145Notes

Reaction equation

HRID 1370145 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]2[NH:13][C:12](=[O:14])[N:11]([C@H:15]3[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17][CH2:16]3)[C:8]2=[N:9][CH:10]=1)#[N:4].[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH2:26]Br>CN(C)C=O>[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH2:26][N:13]1[C:7]2[C:8](=[N:9][CH:10]=[C:5]([C:3]#[N:4])[CH:6]=2)[N:11]([C@H:15]2[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17][CH2:16]2)[C:12]1=[O:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 114703704-(Bromomethyl)-2-chloro-1-methoxybenzeneHCID 178510283HCID 178510283, compound

Product 1

HCID 178490888HCID 178490888, compoundYield 59.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 3.58g) was added portionwise to a solution 6-cyano-3-(trans-4-hydroxycyclohexyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one (21 g) in N,N-dimethylformamide (210 ml) at 0° C., and the mixture was stirred at ambient temperature for an hour. After adding 3-chloro-4-methoxybenzyl bromide (20.1 g) at ambient temperature, the reaction mixture was stirred at same temperature for 3 hours and partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (twice). The combined organic layer was washed with water (twice) and brine, and dried over magnesium sulfate. After evaporation of the solvent, the residue was purified by a silica gel column chromatography eluting with 5% methanol in chloroform and crystallization from ethanol. The crude crystals were suspended in water (400 ml) and stirred at 65° C. for 14 hours to give 1-(3-chloro-4-methoxybenzyl)-6-cyano-3-(trans-4-hydroxycyclohexyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one (19.9 g) as a colorless solid.

Workup

  1. stirringthe reaction mixture was stirred at same temperature for 3 hours
  2. custompartitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate (twice)
  4. washThe combined organic layer was washed with water (twice) and brine
  5. dry with materialdried over magnesium sulfate
  6. customAfter evaporation of the solvent
  7. customthe residue was purified by a silica gel column chromatography
  8. washeluting with 5% methanol in chloroform and crystallization from ethanol
  9. stirringstirred at 65° C. for 14 hours

Sources & evidence

ORD record
ord-b3de3f67c1d24d9dbd45b6b4f862fb2d
Source dataset
uspto-grants-2003_06
Patent number
US06582351B1

Reaction notes

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