4-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1-methyl-1H-quinolin-2-one → 6-[Amino-(6-Chloro-Pyridin-3-yl)-(3-Methyl-3H-Imidazol-4-yl)-Methyl]-4-(3-Chloro-Phenyl)-1-Methyl-1H-Quinolin-2-One

HRID 1384339Notes

Reaction equation

HRID 1384339 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=4)(O)[C:19]4[N:20]([CH3:24])[CH:21]=[N:22][CH:23]=4)[CH:16]=3)[N:11]([CH3:33])[C:10](=[O:34])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.CO.C(Cl)(Cl)Cl.[NH4+:41].[OH-]>S(Cl)(Cl)=O>[NH2:41][C:18]([C:26]1[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=1)([C:19]1[N:20]([CH3:24])[CH:21]=[N:22][CH:23]=1)[C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH3:33])[C:10](=[O:34])[CH:9]=[C:8]2[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1

Participants

4

Reactant 2

HCID 111793634-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1-methyl-1H-quinolin-2-oneHCID 21873181Chloroform methanol ammonium hydroxide

Product 1

HCID 112488556-[Amino-(6-Chloro-Pyridin-3-yl)-(3-Methyl-3H-Imidazol-4-yl)-Methyl]-4-(3-Chloro-Phenyl)-1-Methyl-1H-Quinolin-2-OneYield 50%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

4-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-1-methyl-1H-quinolin-2-one (2 g, 4.08 mmol) was dissolved in 25 ml of thionyl chloride (SOCl2) and stirred at room temperature under an atmosphere of dry N2 for 2 hours. Thiony chloride was removed under reduced pressure. The crude chloride was taken up in toluene and concentrated under vacuum. The resulting solid was dissolved in THF (20 mL) and to this solution was bubbled ammonia gas (NH3) for 30 minutes. The reaction mixture was stirred at ambient temperature under an atmosphere of NH3 for 15 hours. After removal of THF, the product mixture was partitioned between CHCl3 and water. The organic layer was washed, dried over MgSO4 and concentrated under vacuum to give a brown solid. This was chromatographed on silica gel with CHCl3 then MeOH—CHCl3—NH4OH (1:99:0.1) as eluents to afford the titled compound as a white solid (1.065 g, 2.02 mmol, 50% yield).

Workup

  1. customThiony chloride was removed under reduced pressure
  2. concentrationconcentrated under vacuum
  3. dissolutionThe resulting solid was dissolved in THF (20 mL) and to this solution
  4. customwas bubbled ammonia gas (NH3) for 30 minutes
  5. stirringThe reaction mixture was stirred at ambient temperature under an atmosphere of NH3 for 15 hours
  6. customAfter removal of THF
  7. customthe product mixture was partitioned between CHCl3 and water
  8. washThe organic layer was washed
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated under vacuum
  11. customto give a brown solid
  12. customThis was chromatographed on silica gel with CHCl3

Sources & evidence

ORD record
ord-3920addd624944e2a84815242a9186f3
Source dataset
uspto-grants-2001_07
Patent number
US06258824B1

Reaction notes

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