Water → 1-[2-Amino-3-(2,2-dimethyl-propyl)-3H-imidazo[4,5-b]pyridin-5-yl]-2-(4-fluoro-phenyl)-ethane-1,2-dione

HRID 730023Notes

Reaction equation

HRID 730023 reaction equation
[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=[O:8].[Na+].[CH3:12][C:13]([CH3:35])([CH3:34])[CH2:14][N:15]1[C:19]2=[N:20][C:21]([C:24]#[C:25][C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)=[CH:22][CH:23]=[C:18]2[N:17]=[C:16]1[NH2:33].[O-][Mn](=O)(=O)=O.[K+].[O-]S([O-])=O.[Na+].[Na+].[OH2:48]>CC(C)=O.CCOC(C)=O>[NH2:33][C:16]1[N:15]([CH2:14][C:13]([CH3:35])([CH3:34])[CH3:12])[C:19]2=[N:20][C:21]([C:24](=[O:8])[C:25]([C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[O:48])=[CH:22][CH:23]=[C:18]2[N:17]=1

Participants

9

Reactant 6

HCID 962Water2×HCID 24083Sulfuric acid magnesium salt (1:1)HCID 24437Sodium SulfiteHCID 516875Potassium PermanganateHCID 516892Sodium BicarbonateHCID 688980803-(2,2-dimethyl-propyl)-5-(4-fluoro-phenylethynyl)-3H-imidazo[4,5-b]pyridin-2-ylamine

Product 1

HCID 688667071-[2-Amino-3-(2,2-dimethyl-propyl)-3H-imidazo[4,5-b]pyridin-5-yl]-2-(4-fluoro-phenyl)-ethane-1,2-dione

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
42.5 °C

Procedure

Add MgSO4 (82.7 g, 687.05 mmol) and NaHCO3 (14.4 g, 171.41 mmol) in deionized water (1524 mL) over 5 minutes to a stirring solution of 3-(2,2-dimethyl-propyl)-5-(4-fluoro-phenylethynyl)-3H-imidazo[4,5-b]pyridin-2-ylamine (110.76 g, 343.57 mmol) in acetone (3665 mL). Add Hyflo Super Cel® (171.1 g) followed by KMnO4 (108.6 g, 687.21 mmol). Heat at 40-45° C. for 3 hours and then cool to room temperature. Add saturated aqueous Na2SO3 (1,800 mL) followed by EtOAc (3,500 mL) and water (3,500 mL). Filter through bed of Hyflo Super Cel® washing with a mixture of 9% MeOH/EtOAc (2,860 mL). Separate layers of filtrate, back-extract aqueous layer 2×2,750 mL EtOAc. Combine organic extracts, wash 2×2,380 mL saturated aqueous sodium chloride (4760 mL), and dry over Na2SO4. Filter, then concentrate under reduced pressure to provide a dark red-brown solid (185 g). Add acetone (650 mL), filter suspension, wash collected solid 3×167 mL MTBE (501 mL), and dry under reduced pressure at 45° C. to provide 106.79 g (88%) of the desired compound as a light yellow solid.

Workup

  1. temperaturecool to room temperature
  2. filtrationFilter through bed of Hyflo Super Cel®
  3. washwashing with a mixture of 9% MeOH/EtOAc (2,860 mL)
  4. extractionSeparate layers of filtrate, back-extract aqueous layer 2×2,750 mL EtOAc
  5. washCombine organic extracts, wash 2×2,380 mL saturated aqueous sodium chloride (4760 mL)
  6. dry with materialdry over Na2SO4
  7. filtrationFilter
  8. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-283c525fcd4548609c30ab32160d8ab0
Source dataset
uspto-grants-2009_09
Patent number
US07582652B2

Reaction notes

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