(4-chloro-2-(dimethylamino)-3-phenylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol → 4-Chloro-6-((4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-N,N-dimethyl-3-phenylquinolin-2-amine

HRID 1478529Notes

Reaction equation

HRID 1478529 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([C:14]3[N:18]([CH3:19])[CH:17]=[N:16][CH:15]=3)O)[CH:10]=2)[N:5]=[C:4]([N:27]([CH3:29])[CH3:28])[C:3]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[Cu]C#N>CN1C(=O)CCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:20]3[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=3)[C:14]3[N:18]([CH3:19])[CH:17]=[N:16][CH:15]=3)[CH:10]=2)[N:5]=[C:4]([N:27]([CH3:29])[CH3:28])[C:3]=1[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

4

Reactant 2

HCID 118005585(4-chloro-2-(dimethylamino)-3-phenylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanolHCID 178418546HCID 178418546, compound

Product 1

HCID 1180055694-Chloro-6-((4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-N,N-dimethyl-3-phenylquinolin-2-amine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To (4-chloro-2-(dimethylamino)-3-phenylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol (83.6 mg, 0.166 mmol, Example 90) in NMP (1.5 mL), was added copper (I) cyanide (16.4 mg, 0.183 mmol). The mixture was heated by microwave irradiation for 10 minutes at 120° C. The mixture was partitioned between MTBE and saturated aqueous NH4OH. The organic phase was washed with water. The organic phase was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by RP-HPLC (10-90% CH3CN—H2O, 0.1% TFA) and fractions were converted to the corresponding free base by extraction from saturated aqueous NaHCO3 with DCM. Further purification by flash column chromatography (silica gel, 10-70% acetone-DCM) afforded the title compound. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J=1.96 Hz, 1H), 7.76 (d, J=8.80 Hz, 1H), 7.55 (br. s., 1H), 7.43-7.50 (m, 2H), 7.34-7.42 (m, 4H), 7.30 (d, J=8.56 Hz, 2H), 7.12 (d, J=8.56 Hz, 2H), 6.48 (br. s., 1H), 5.45 (s, 1H), 3.37 (s, 3H), 2.71 (s, 6H); MS m/e 487.0 (M+H)+.

Workup

  1. customThe mixture was partitioned between MTBE and saturated aqueous NH4OH
  2. washThe organic phase was washed with water
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by RP-HPLC (10-90% CH3CN—H2O, 0.1% TFA) and fractions
  7. extractionwere converted to the corresponding free base by extraction from saturated aqueous NaHCO3 with DCM
  8. customFurther purification by flash column chromatography (silica gel, 10-70% acetone-DCM)

Sources & evidence

ORD record
ord-01ccb6f55c7a4578a717ecaf3c4b92b0
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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