Sodium Hydroxide → 1-ethyl-7-(hydroxymethyl)-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 587610Notes

Reaction equation

HRID 587610 reaction equation
C([O:4][CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[N:12]([C:18]3[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=3)[C:13](=[O:17])[N:14]([CH2:15][CH3:16])[C:7]=12)(=O)C.[OH-].[Na+].[NH4+:27].[Cl-]>CCO>[CH2:15]([N:14]1[C:7]2[C:8](=[N:9][CH:10]=[CH:11][C:6]=2[CH2:5][OH:4])[N:12]([C:18]2[CH:23]=[CH:22][C:21]([O:24][C:13]3[N:12]([CH3:18])[C:8]4=[N:9][CH:10]=[CH:11][CH:6]=[C:7]4[N:27]=3)=[CH:20][CH:19]=2)[C:13]1=[O:17])[CH3:16]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 58577626[1-ethyl-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl]methyl acetate

Product 1

HCID 547713221-ethyl-7-(hydroxymethyl)-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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of [1-ethyl-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl]methyl acetate (150 mg) and EtOH (3 mL) was added 1 N NaOH (2 mL) at 0° C. The mixture was stirred at 0° C. for 30 min, treated with saturated NH4Cl solution, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DMA (4 mL) and KOtBu (52 mg) was added at room temperature. The mixture was stirred for 2 min, and then 3-methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (97 mg) was added. The mixture was stirred at 150° C. for 30 min, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was chromatographed on NH-silica gel eluting with AcOEt/MeOH=20/1. The product was crystallized from AcOEt/Hexane to give 1-ethyl-7-(hydroxymethyl)-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 (46 mg).

Workup

  1. extractionextracted with AcOEt
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DMA (4 mL)
  5. additionKOtBu (52 mg) was added at room temperature
  6. stirringThe mixture was stirred for 2 min
  7. addition3-methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (97 mg) was added
  8. stirringThe mixture was stirred at 150° C. for 30 min
  9. additiontreated with water
  10. extractionextracted with AcOEt
  11. dry with materialThe organic layer was dried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was chromatographed on NH-silica gel eluting with AcOEt/MeOH=20/1
  14. customThe product was crystallized from AcOEt/Hexane

Sources & evidence

ORD record
ord-5f3ecbf958024c6b8cdb30049f380135
Source dataset
uspto-grants-2016_01
Patent number
US09226921B2

Reaction notes

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