Water → 1-ethyl-6-fluoro-3-(4-hydroxyphenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 1430046Notes

Reaction equation

HRID 1430046 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([NH2:22])=[CH:20][C:19]([F:23])=[CH:18][N:17]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.C(N1C=CN=C1)(N1[CH:30]=[CH:29]N=C1)=O.[C:36]([O-:39])([O-])=O.[Cs+].[Cs+].O>COCCOC>[CH2:29]([N:22]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([F:23])[CH:20]=2)[N:15]([C:12]2[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=2)[C:36]1=[O:39])[CH3:30]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 682631,1'-Carbonyldiimidazole2×HCID 58577701N2-[4-(benzyloxy)phenyl]-5-fluoropyridine-2,3-diamine

Product 1

HCID 585773231-ethyl-6-fluoro-3-(4-hydroxyphenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneYield 69.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N2-[4-(benzyloxy)phenyl]-5-fluoropyridine-2,3-diamine (0.85 g) and 1,1′-carbonylbis(1H-imidazole) (0.45 g) in DME (10 mL) was stirred at 100° C. for 4 h, and then Cs2CO3 (0.90 g) and 1,1′-carbonylbis(1H-imidazole) (0.892 g) were added successively. The mixture was stirred at 100° C. for 10 min, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DMF (10 mL), and then Cs2CO3 (3.58 g) and iodoethane (1.29 g) were added successively. The mixture was stirred at 100° C. for 2 h, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was dissolved in EtOH (30 mL), and Pd/C (1.5 g) was added. Under H2 atmosphere, the mixture was stirred at room temperature for 30 min, filtered and evaporated. The residue was chromatographed on silica gel eluting with AcOEt/Hexane to give the title compound (0.52 g).

Workup

  1. stirringThe mixture was stirred at 100° C. for 10 min
  2. extractionextracted with AcOEt
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in DMF (10 mL)
  6. additionCs2CO3 (3.58 g) and iodoethane (1.29 g) were added successively
  7. stirringThe mixture was stirred at 100° C. for 2 h
  8. additiontreated with water
  9. extractionextracted with AcOEt
  10. dry with materialThe organic layer was dried over MgSO4
  11. concentrationconcentrated in vacuo
  12. dissolutionThe residue was dissolved in EtOH (30 mL)
  13. additionPd/C (1.5 g) was added
  14. stirringUnder H2 atmosphere, the mixture was stirred at room temperature for 30 min
  15. filtrationfiltered
  16. customevaporated
  17. customThe residue was chromatographed on silica gel eluting with AcOEt/Hexane

Sources & evidence

ORD record
ord-c38759699ee14fb58fce2ff59c0f3f89
Source dataset
uspto-grants-2015_01
Patent number
US08940758B2

Reaction notes

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