Toluene → [2-(2-Aziridin-1-ylethoxy)-4-chloro-3-phenylquinolin-6-yl](4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 1478519Notes

Reaction equation

HRID 1478519 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[C:21](Cl)[C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:19]3[Cl:33])([C:10]2[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=2)[OH:9])=[CH:4][CH:3]=1.[N:34]1([CH2:37][CH2:38][OH:39])[CH2:36][CH2:35]1.C1(C)C=CC=CC=1.[H-].[Na+]>CCOC(C)=O>[N:34]1([CH2:37][CH2:38][O:39][C:21]2[C:20]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[C:19]([Cl:33])[C:18]3[C:23](=[CH:24][CH:25]=[C:16]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)([C:10]4[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=4)[OH:9])[CH:17]=3)[N:22]=2)[CH2:36][CH2:35]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 140741-AziridineethanolHCID 24758Sodium hydrideHCID 90100965(4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol

Product 1

HCID 118005524[2-(2-Aziridin-1-ylethoxy)-4-chloro-3-phenylquinolin-6-yl](4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol (100 mg, 0.202 mmol, Example 65), 2-(aziridin-1-yl)ethanol (16.2 μL, 0.20 mmol), toluene (2 mL), and sodium hydride (60% dispersion in mineral oil, 20.2 mg, 0.51 mmol) were combined in a round bottom flask under an N2 atmosphere. The reaction solution was heated to reflux and refluxed overnight, cooled and stirred at room temperature an additional night before workup. Reaction contents were transferred to a separatory funnel with EtOAc dilution, and extracted with saturated, aqueous NH4Cl then saturated, aqueous NaHCO3 solutions. The organic phase was separated then dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/MeOH) to afford the title compound. MS (ESI): mass calcd. for C30H26Cl2N4O2, 544.1; m/z found, 545.1 [M+H]+; 1H NMR (600 MHz, CD3OD) δ ppm 8.05 (d, J=2.0 Hz, 1H), 7.74 (d, J=8.7 Hz, 1H), 7.61-7.57 (m, 2H), 7.40-7.35 (m, 2H), 7.35-7.31 (m, 1H), 7.28-7.23 (m, 6H), 6.18 (d, J=1.1 Hz, 1H), 4.51-4.44 (m, 2H), 3.37 (s, 3H), 2.50-2.39 (m, 2H), 1.48-1.37 (m, 2H), 0.97-0.94 (m, 2H).

Workup

  1. temperatureThe reaction solution was heated
  2. temperatureto reflux
  3. temperaturerefluxed overnight
  4. temperaturecooled
  5. customReaction contents
  6. extractionextracted with saturated, aqueous NH4Cl
  7. customThe organic phase was separated
  8. dry with materialthen dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by flash column chromatography (silica gel, 0-10% DCM/MeOH)

Sources & evidence

ORD record
ord-e89b08f3d36b42f09b1e5cedd976d9e3
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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