Sodium hydride → 1-ethyl-6-methoxy-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 1044248Notes

Reaction equation

HRID 1044248 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1S(C)(=O)=O.[CH2:15]([N:17]1[C:25]2[C:20](=[N:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]([C:28]2[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=2)[C:18]1=[O:35])[CH3:16].[H-].[Na+]>CN(C=O)C>[CH2:15]([N:17]1[C:25]2[C:20](=[N:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:3]3[N:2]([CH3:1])[C:6]4=[N:7][CH:8]=[CH:9][CH:10]=[C:5]4[N:4]=3)=[CH:30][CH:29]=2)[C:18]1=[O:35])[CH3:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 585773681-ethyl-3-(4-hydroxyphenyl)-6-methoxy-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneHCID 585773713-Methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine

Product 1

HCID 547710931-ethyl-6-methoxy-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneYield 15.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 3-methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (67 mg) and 1-ethyl-3-(4-hydroxyphenyl)-6-methoxy-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (75 mg) in DMF (3 mL) was added NaH (13 mg) at room temperature, and the mixture was stirred at 150° C. under microwave irradiation for 2 h. The mixture was partitioned between water and AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (dry charge, NH silica gel, eluted with 50%-100% AcOEt in hexane) and column chromatography (dry charge, silica gel, eluted with 50%-100% AcOEt in hexane), and recrystallized from MeOH to give 1-ethyl-6-methoxy-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (17 mg) as white crystals.

Workup

  1. customThe mixture was partitioned between water and AcOEt
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (dry charge, NH silica gel, eluted with 50%-100% AcOEt in hexane) and column chromatography (dry charge, silica gel, eluted with 50%-100% AcOEt in hexane)
  7. customrecrystallized from MeOH

Sources & evidence

ORD record
ord-17a2e63bec4544e593a0a413f799d726
Source dataset
uspto-grants-2013_10
Patent number
US08563575B2

Reaction notes

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