Sodium hydride → 6-(difluoromethoxy)-1-ethyl-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 587573Notes

Reaction equation

HRID 587573 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.[F:15][CH:16]([F:37])[O:17][C:18]1[CH:19]=[C:20]2[N:26]([CH2:27][CH3:28])[C:25](=[O:29])[N:24]([C:30]3[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=3)[C:21]2=[N:22][CH:23]=1.[H-].[Na+]>CN(C=O)C>[F:37][CH:16]([F:15])[O:17][C:18]1[CH:19]=[C:20]2[N:26]([CH2:27][CH3:28])[C:25](=[O:29])[N:24]([C:30]3[CH:35]=[CH:34][C:33]([O:36][C:3]4[N:2]([CH3:1])[C:6]5=[N:7][CH:8]=[CH:9][CH:10]=[C:5]5[N:4]=4)=[CH:32][CH:31]=3)[C:21]2=[N:22][CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 585773713-Methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridineHCID 585777676-(difluoromethoxy)-1-ethyl-3-(4-hydroxyphenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 585775276-(difluoromethoxy)-1-ethyl-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 46.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of 3-methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (62 mg) and 6-(difluoromethoxy)-1-ethyl-3-(4-hydroxyphenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (86 mg) in DMF (3 mL) was added NaH (13 mg) at room temperature, and the mixture was stirred at 180° C. under microwave irradiation for 30 min. 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 recrystallized from AcOEt/hexane to give 6-(difluoromethoxy)-1-ethyl-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 (56 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)
  7. customrecrystallized from AcOEt/hexane

Sources & evidence

ORD record
ord-8fc6998cbdbc40bd847716eecc50657a
Source dataset
uspto-grants-2016_01
Patent number
US09226921B2

Reaction notes

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