Hydrochloric Acid → (4-Chloro-3-phenylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 627544Notes

Reaction equation

HRID 627544 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=O)[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[C:5]2O.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([C:29]2[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=2)=[O:28])=[CH:23][CH:22]=1.[Li]CCCC.[ClH:40]>O1CCCC1>[Cl:40][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:27]([C:24]3[CH:23]=[CH:22][C:21]([Cl:20])=[CH:26][CH:25]=3)([C:29]3[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=3)[OH:28])[CH:3]=2)[N:8]=[CH:7][C:6]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11521405(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone2×HCID 867160566-Bromo-4-hydroxy-3-phenylquinolin-2(1H)-one2×HCID 178418339Butyllithium

Product 1

HCID 86716106(4-Chloro-3-phenylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

In a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 6-bromo-4-chloro-3-phenylquinoline (460 mg, 1.44 mmol, Intermediate 3, step c), (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (266 mg, 1.21 mmol, Intermediate 18, step b) in tetrahydrofuran (20 mL). This solution was cooled to −78° C., followed by the addition of n-BuLi (0.624 mL, 1.56 mmol, 2.5M in hexane) dropwise. The mixture was gradually warmed to room temperature. After 4 hours stirring, 1.0 M HCl was added until pH 6-7. After removal of solvent under vacuum, the residue was purified by flash column chromatography (silica gel column, 100:0˜15:1 EtOAc/petroleum ether) to give the title compound as a white solid. 1H NMR (300 MHz, MeOH-d4) δ=8.83 (s, 1H), 8.39 (d, J=1.5 Hz, 1H), 8.12 (d, J=9.0 Hz, 1H), 7.88 (dd, J=1.9, 8.9 Hz, 1H), 7.75 (s, 1H), 7.46-7.62 (m, 5H), 7.41 (s, 4H), 6.35 (s, 1H), 3.51 (s, 3H); MS m/e 460 [M+H]+.

Workup

  1. customIn a 100-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureThe mixture was gradually warmed to room temperature
  4. customAfter removal of solvent under vacuum
  5. customthe residue was purified by flash column chromatography (silica gel column, 100:0˜15:1 EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-45eb803c4e0845a3a312f4a567a5ef1f
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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