(2,4-Dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone → Cyclopropyl(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 526854Notes

Reaction equation

HRID 526854 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Cl:6][C:7]1[C:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:15]([Cl:23])[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:24]([C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)=[O:25])[CH:13]=2)[N:8]=1>C1COCC1>[CH:1]1([C:24]([C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([Cl:6])[C:16]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[C:15]3[Cl:23])([C:26]2[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=2)[OH:25])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 118006377(2,4-Dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone2×HCID 178418630HCID 178418630, compound

Product 1

HCID 118006470Cyclopropyl(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Cyclopropylmagnesium bromide (0.5 M in THF, 0.6 mL, 0.3 mmol) was added dropwise to a solution of (2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (57.3 mg, 0.15 mmol, Intermediate 2: step b) in THF (1 mL) at 0° C. The mixture was stirred at 0° C. for 5 minutes, then the ice bath was removed and the mixture was stirred for 3 hours. The reaction was quenched by the addition of saturated aqueous NH4Cl and was diluted with water. The mixture was extracted three times with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 0-4% MeOH-DCM) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J=1.71 Hz, 1H), 8.03 (d, J=8.80 Hz, 1H), 7.66 (dd, J=1.96, 8.80 Hz, 1H), 7.46-7.61 (m, 4H), 7.39-7.46 (m, 2H), 7.30 (d, J=0.98 Hz, 1H), 5.82 (s, 1H), 3.14 (s, 3H), 1.63-1.74 (m, 1H), 0.53-0.71 (m, 2H), 0.19-0.42 (m, 2H); MS m/e 424.0 (M+H)+.

Workup

  1. customthe ice bath was removed
  2. stirringthe mixture was stirred for 3 hours
  3. customThe reaction was quenched by the addition of saturated aqueous NH4Cl
  4. additionwas diluted with water
  5. extractionThe mixture was extracted three times with EtOAc
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (silica gel, 0-4% MeOH-DCM)

Sources & evidence

ORD record
ord-09d6006e906045f3ad04a72c4ff2b3d7
Source dataset
uspto-grants-2016_05
Patent number
US09346782B2

Reaction notes

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