Ethyl Acetate → HCID 11705579, compound

HRID 730015Notes

Reaction equation

HRID 730015 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:13][C:12]([C:14]2[N:19]=[C:18]([NH:20][CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:17]([N+:26]([O-])=O)=[CH:16][CH:15]=2)=[C:11]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:10]=1.O.O.[Sn](Cl)Cl.[N:40]#[C:41]Br.C(OCC)(=O)C>C(O)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:13][C:12]([C:14]2[N:19]=[C:18]3[N:20]([CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:41]([NH2:40])=[N:26][C:17]3=[CH:16][CH:15]=2)=[C:11]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:10]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10476Cyanogen BromideHCID 61436Stannous chloride dihydrateHCID 68866772HCID 68866772, compound

Product 1

HCID 11705579HCID 11705579, compoundYield 82.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

Dissolve {6-[2-(2-chloro-6-fluoro-phenyl)-5-phenyl-3H-imidazol-4-yl]-3-nitro-pyridin-2-yl}-(2,2-dimethylpropyl)-amine (240 mg, 0.50 mmol) in 100% ethanol (10 mL) and add tin(II) dichloride dihydrate (564 mg, 2.50 mmol, 5.0 equiv). Heat the reaction mixture until starting material is consumed. Cool the reaction solution to room temperature, quench slowly with saturated aqueous NaHCO3. Add Celite® to the quenched reaction and filter the suspension on a Celite® pad with water and ethyl acetate washes. Separate the layers and wash the organic layer with saturated aqueous NaCl. Dry the organic layer with Na2SO4, filter, and concentrate under reduced pressure. Add 10% aqueous ethanol and cyanogen bromide (106 mg, 1.00 mmol, 2.0 equiv) to the resulting solid and stir overnight. Quench the reaction with saturated aqueous NaHCO3 (20 mL). Add ethyl acetate and water to dissolve all solids. Wash the organic layer three times with saturated aqueous NaCl, dry with Na2SO4, filter, and concentrate under reduced pressure. Subject the residue to medium pressure silica gel chromatography eluting with a gradient of 1.5-3% (2M ammonia in MeOH)/CH2Cl2 to provide 5-[2-(2-Chloro-6-fluoro-phenyl)-5-phenyl-3H-imidazol-4-yl]-3-(2,2-dimethylpropyl)-3H-imidazo[4,5-b]pyridin-2-ylamine as a yellow-green solid (196 mg, 60% yield).

Workup

  1. temperatureHeat the reaction mixture
  2. customis consumed
  3. customquench slowly with saturated aqueous NaHCO3
  4. customAdd Celite® to the quenched reaction
  5. filtrationfilter the suspension on a Celite® pad with water and ethyl acetate washes
  6. customSeparate the layers
  7. washwash the organic layer with saturated aqueous NaCl
  8. dry with materialDry the organic layer with Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate under reduced pressure
  11. customQuench
  12. customthe reaction with saturated aqueous NaHCO3 (20 mL)
  13. washWash the organic layer three times with saturated aqueous NaCl
  14. dry with materialdry with Na2SO4
  15. filtrationfilter
  16. concentrationconcentrate under reduced pressure
  17. washeluting with a gradient of 1.5-3% (2M ammonia in MeOH)/CH2Cl2

Sources & evidence

ORD record
ord-f31b98aa0946493da01c13109f773cd6
Source dataset
uspto-grants-2009_09
Patent number
US07582652B2

Reaction notes

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