Acetic Acid → 5-Chloro-2,7-dimethyl-1H-imidazo[4,5-b]pyridine

HRID 1890623Notes

Reaction equation

HRID 1890623 reaction equation
[NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([CH3:11])[CH:5]=[C:4]([Cl:12])[N:3]=1.O.O.[Sn](Cl)Cl.[OH-].[Na+].[C:20](O)(=O)[CH3:21].C(=O)([O-])[O-].[Na+].[Na+].N>C(O)C.C(OCC)(=O)C>[Cl:12][C:4]1[N:3]=[C:2]2[N:1]=[C:20]([CH3:21])[NH:8][C:7]2=[C:6]([CH3:11])[CH:5]=1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 222AmmoniaHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 61436Stannous chloride dihydrateHCID 707010046-Chloro-4-methyl-3-nitropyridin-2-amine

Product 1

HCID 223884515-Chloro-2,7-dimethyl-1H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

2-Amino-6-chloro-4-methyl-3-nitropiridine (1.2 g, 6.40 mmol) synthesized according to the method described in WO98/02442 was dissolved in ethanol (65 mL), and tin(II) chloride dihydrate (4.33 g, 19.2 mmol) was added, followed by stirring at 75° C. for 2 hours. The reaction mixture was diluted with ethyl acetate and was added with 3 mol/L aqueous sodium hydroxide solution. The unsoluble material was filtered out through Celite, and washed with ethyl acetate. The filtrate was sequentially washed with water, saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Next, polyphosphoric acid (15.3 g) and acetic acid (1.72 mL, 30.0 mmol) was added to the residue, and was stirred for 80° C. for 3 hours. The reaction mixture was moved to ice water and sodium carbonate (11.4 g, 0.108 mol) was added in a little portion while stirring. Then, 28% aqueous ammonia solution was added to the residue to control the pH to 9 and the mixture was stirred for 1 hour. Precipitated crude crystals were collected by filtration, and were washed with water, and the obtained crystals were dried in vacuo at 40° C. overnight to obtain Compound P38 (395 mg, 34%).

Workup

  1. filtrationThe unsoluble material was filtered out through Celite
  2. washwashed with ethyl acetate
  3. washThe filtrate was sequentially washed with water, saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. stirringwas stirred for 80° C. for 3 hours
  7. additionwas added in a little portion
  8. stirringwhile stirring
  9. stirringthe mixture was stirred for 1 hour
  10. customPrecipitated crude crystals
  11. filtrationwere collected by filtration
  12. washwere washed with water
  13. customthe obtained crystals were dried in vacuo at 40° C. overnight
  14. customto obtain Compound P38 (395 mg, 34%)

Sources & evidence

ORD record
ord-353b4a496194476d972460b8ccd840dd
Source dataset
uspto-grants-2013_08
Patent number
US08507484B2

Reaction notes

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