Potassium Carbonate → 4-(benzyloxy)-6-(3,4-dimethoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridine

HRID 2209000Notes

Reaction equation

HRID 2209000 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[N:15]([CH3:18])[CH:16]=[N:17][C:13]=2[CH:12]=[C:11](Cl)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([O-:23])([O-])=O.[K+].[K+].COOB([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)OOC.[C:39]([O-])(O)=[O:40].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCOC(C)=O.O.CC(O)C.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[C:14]2[N:15]([CH3:18])[CH:16]=[N:17][C:13]=2[CH:12]=[C:11]([C:36]2[CH:35]=[CH:34][C:33]([O:40][CH3:39])=[C:38]([O:23][CH3:20])[CH:37]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 208206864-Benzyloxy-6-chloro-3-methyl-imidazo[4,5-c]pyridineHCID 86637092Dimethoxyphenyl boronic acid

Product 1

HCID 1178430324-(benzyloxy)-6-(3,4-dimethoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridine

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-(benzyloxy)-6-chloro-3-methyl-3H-imidazo[4,5-c]pyridine 2.25 (0.54 g, 1.97 mmol), K2CO3 (0.68 g, 4.93 mmol), Pd(dppf)Cl2 (0.07 g, 0.1 mmol), and dimethoxy phenyl boronic acid (0.65 g, 3.55 mmol) under N2 was added toluene, iPrOH, and water (2:1:1, 10 mL), and the reaction was heated to 100° C. for 5 hrs. The reaction was cooled and EtOAc (40 mL)/NaHCO3 (20 mL) were added, the layers were separated and the aqueous was extracted with EtOAc (2×25 mL). The combined organics were washed with brine (50 mL), dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (EtOAc 0-->5% MeOH gradient) to afford 4-(benzyloxy)-6-(3,4-dimethoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridine 2.26.

Workup

  1. temperatureThe reaction was cooled
  2. customthe layers were separated
  3. extractionthe aqueous was extracted with EtOAc (2×25 mL)
  4. washThe combined organics were washed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (EtOAc 0-->5% MeOH gradient)

Sources & evidence

ORD record
ord-30f13ea621c94cadaf261a85cfd8ad07
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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