Sodium hydride → 1-ethyl-7-methyl-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 4-oxide

HRID 587606Notes

Reaction equation

HRID 587606 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]([O-:27])[CH:22]=[CH:23][C:24]=2[CH3:26])[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+].[Cl-].[Cl-].[Ca+2]>CC(N(C)C)=O>[CH2:15]([N:17]1[C:25]2[C:20](=[N+:21]([O-:27])[CH:22]=[CH:23][C:24]=2[CH3:26])[N:19]([C:28]2[CH:29]=[CH:30][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:32][CH:33]=2)[C:18]1=[O:35])[CH3:16]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 5284359Calcium ChlorideHCID 585773713-Methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridineHCID 679932051-ethyl-3-(4-hydroxyphenyl)-7-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one 4-oxide

Product 1

HCID 585775561-ethyl-7-methyl-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 4-oxide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Tetrabutylammonium fluoride (0.566 mL) was added to a solution of 1-ethyl-7-methyl-3-(4-{[tris(1-methylethyl)silyl]oxy}phenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one 4-oxide (250 mg) in THF (5 mL) at room temperature. The mixture was stirred at room temperature under a dry atmosphere (CaCl2 tube) for 30 min. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 0%-100% EtOAc in hexane) to give 1-ethyl-3-(4-hydroxyphenyl)-7-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one 4-oxide (170 mg) as a colorless solid. 3-Methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (126 mg) was added to a solution of 1-ethyl-3-(4-hydroxyphenyl)-7-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one 4-oxide (170 mg) and NaH (23.83 mg) in DMA (1 mL) at room temperature. The mixture was stirred at 150° C. under a dry atmosphere (CaCl2 tube) for 30 min. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 50%-100% EtOAc in hexane) to give 1-ethyl-7-methyl-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 4-oxide as colorless crystals.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue was purified by column chromatography (NH silica gel, eluted with 50%-100% EtOAc in hexane)

Sources & evidence

ORD record
ord-74a7e76c6201472384d70af74493ebe8
Source dataset
uspto-grants-2016_01
Patent number
US09226921B2

Reaction notes

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