(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone → (2-Chloro-3-phenylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 1478531Notes

Reaction equation

HRID 1478531 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:12])[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[CH:5]2.[Li]CCCC.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:33]2[N:37]([CH3:38])[CH:36]=[N:35][CH:34]=2)=[O:32])=[CH:27][CH:26]=1>O1CCCC1>[Cl:12][C:7]1[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:31]([C:28]3[CH:29]=[CH:30][C:25]([Cl:24])=[CH:26][CH:27]=3)([C:33]3[N:37]([CH3:38])[CH:36]=[N:35][CH:34]=3)[OH:32])[CH:3]=2)[N:8]=1

Participants

5

Reactant 3

HCID 11521405(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone2×HCID 132001916-Bromo-2-chloro-3-phenylquinoline2×HCID 178418339Butyllithium

Product 1

HCID 118005546(2-Chloro-3-phenylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a 50-mL round-bottom flask containing a solution of 6-bromo-2-chloro-3-phenylquinoline (210 mg, 0.66 mmol, Intermediate 31: step b) in tetrahydrofuran (10 mL) was added 2.5 M n-BuLi in hexanes (0.29 mL, 0.72 mmol) dropwise with stirring at −78° C. After 45 minutes at −78° C., a solution of (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (132 mg, 0.60 mmol, Intermediate 8: step b) in tetrahydrofuran (2 mL) was added dropwise. The resulting solution was stirred at −78° C. for an additional 2 hours, then quenched with 30 mL of aqueous NH4Cl and extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by FCC (20:1 DCM/MeOH) to provide the title compound as a white solid. MS (ES): mass calcd. for C26H19Cl2N3O, 459.1; m/z found, 460.0 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.96 (d, J=3.9 Hz, 1H), 8.33 (s, 1H), 8.05 (d, J=6.0 Hz, 1H), 7.94 (s, 1H), 7.88 (d, J=6.6 Hz, 1H), 7.42-7.56 (m, 9H), 6.93 (s, 1H), 3.71 (s, 3H).

Workup

  1. stirringThe resulting solution was stirred at −78° C. for an additional 2 hours
  2. customquenched with 30 mL of aqueous NH4Cl
  3. extractionextracted with ethyl acetate (2×30 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by FCC (20:1 DCM/MeOH)

Sources & evidence

ORD record
ord-5a0a7f1341964116be45e019056209f4
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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