Thionyl Chloride → 6-[Amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1H-quinolin-2-one

HRID 1384371Notes

Reaction equation

HRID 1384371 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)([C:20]4[N:21]([CH3:25])[CH:22]=[N:23][CH:24]=4)O)[CH:16]=3)[N:11]=[C:10]([O:33]C)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.CO.C(Cl)(Cl)Cl.[NH4+:45].[OH-]>C1(C)C=CC=CC=1>[NH2:45][C:18]([C:26]1[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=1)([C:20]1[N:21]([CH3:25])[CH:22]=[N:23][CH:24]=1)[C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:33])[CH:9]=[C:8]2[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 12016674[4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanolHCID 21873181Chloroform methanol ammonium hydroxide

Product 1

HCID 120507296-[Amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1H-quinolin-2-oneYield 88%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To [4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanol (20.95 g, 42.76 mmol) in toluene (150 ml) under an atmosphere of dry N2 was added thionyl chloride (31.19 ml, 427 mmol) dropwise. The reaction mixture was heated at 85° C. for 15 hours. Solvent and the excess thionyl chloride were removed under reduced pressure. The crude chloride was taken up in toluene and concentrated under vacuum. The resulting solid was dissolved in THF (10 ml) and to this solution at −78° C. was bubbled ammonia gas (NH3) for 10 minutes. The reaction mixture was stirred at ambient temperature under an atmosphere of N2 for additional 1.5 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 the crude product. It was chromatographed on silica gel with CHCl3 then MeOH—CHCl3—NH4OH (2:98:0.1 to 7:93:0.1) as eluents to afford the titled compound (17.89 g, 88% yield).

Workup

  1. customSolvent and the excess thionyl chloride were removed under reduced pressure
  2. concentrationconcentrated under vacuum
  3. dissolutionThe resulting solid was dissolved in THF (10 ml) and to this solution at −78° C.
  4. customwas bubbled ammonia gas (NH3) for 10 minutes
  5. customAfter removal of THF
  6. customthe product mixture was partitioned between CHCl3 and water
  7. washThe organic layer was washed
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under vacuum
  10. customto give the crude product
  11. customIt was chromatographed on silica gel with CHCl3

Sources & evidence

ORD record
ord-f701811eaec046698f157ce0517dae97
Source dataset
uspto-grants-2001_07
Patent number
US06258824B1

Reaction notes

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