Cyanogen Bromide → HCID 68870531, compound

HRID 730018Notes

Reaction equation

HRID 730018 reaction equation
[F: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][C@H:21]([CH3:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:17]([N+:27]([O-])=O)=[CH:16][CH:15]=2)=[C:11]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[N:10]=1.O.O.[Sn](Cl)Cl.[N:42]#[C:43]Br>C(O)C>[F: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]([C@H:21]([CH3:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:43]([NH2:42])=[N:27][C:17]3=[CH:16][CH:15]=2)=[C:11]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[N:10]=1

Participants

5

Reactant 3

HCID 10476Cyanogen BromideHCID 61436Stannous chloride dihydrateHCID 68867456HCID 68867456, compound

Product 1

HCID 68870531HCID 68870531, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Dissolve {6-[2-(2,6-difluoro-phenyl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-3-nitro-pyridin-2-yl}-(1(R),2,2-trimethyl-propyl)-amine (673 mg, 1.4 mmol) in 100% ethanol (15 mL) and add tin(II) dichloride dihydrate (1.5 g, 6.8 mmol, 5 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, washing with water and ethyl acetate. Separate the layers and wash the organic layer with saturated aqueous NaCl. Dry the organic layer with Na2SO4, filter, and concentrated under reduced pressure. Add 10% aqueous ethanol (14 mL) and cyanogen bromide (216 mg, 2.04 mmol, 1.5 equiv) to the residue and stir overnight. Quench with saturated aqueous NaHCO3 (20 mL). Add ethyl acetate and water to dissolve all solids. Wash the organic layer is 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-(2,6-difluoro-phenyl)-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-3-(1(R),2,2-trimethyl-propyl)-3H-imidazo[4,5-b]pyridin-2-ylamine as a tan glass (289 mg, 43% 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
  6. washwashing with water and ethyl acetate
  7. customSeparate the layers
  8. washwash the organic layer with saturated aqueous NaCl
  9. dry with materialDry the organic layer with Na2SO4
  10. filtrationfilter
  11. concentrationconcentrated under reduced pressure
  12. customQuench with saturated aqueous NaHCO3 (20 mL)
  13. dissolutionAdd ethyl acetate and water to dissolve all solids
  14. washWash the organic layer
  15. dry with materialdry with Na2SO4
  16. filtrationfilter
  17. concentrationconcentrate under reduced pressure
  18. washeluting with a gradient of 1.5-3% (2M ammonia in MeOH)/CH2Cl2

Sources & evidence

ORD record
ord-22d09da2c3fa4247a9c0e426b47d161f
Source dataset
uspto-grants-2009_09
Patent number
US07582652B2

Reaction notes

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