Ammonium Chloride → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)bis(1-methyl-1H-imidazol-5-yl)methanol

HRID 926644Notes

Reaction equation

HRID 926644 reaction equation
[Li]CCCC.[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](C(C3C(C)=NC(C)=CC=3)O)[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1.[CH3:40][N:41]1[C:45]([C:46]([C:48]2[N:52]([CH3:53])[CH:51]=[N:50][CH:49]=2)=[O:47])=[CH:44][N:43]=[CH:42]1.[NH4+].[Cl-]>C1COCC1.O>[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:46]([C:45]3[N:41]([CH3:40])[CH:42]=[N:43][CH:44]=3)([C:48]3[N:52]([CH3:53])[CH:51]=[N:50][CH:49]=3)[OH:47])[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:37])[F:38])=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 22048478Bis(1-methyl-1H-imidazol-5-yl)methanone2×HCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol2×HCID 178418339Butyllithium

Product 1

HCID 118006553(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)bis(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

n-BuLi (1.6 M in hexanes, 0.34 mL, 0.56 mmol) was added dropwise to a mixture of 6-bromo-2,4-dichloro-3-(4-(trifluoromethyl)benzyl)quinoline (0.20 g, 0.467 mmol, Intermediate 12: step d) and bis(1-methyl-1H-imidazol-5-yl)methanone (0.097 g, 0.513 mmol, Intermediate 55: step b) in dry THF at −78° C. over a 30 minute period. Stirring was continued at −78° C. for 10 minutes. The reaction mixture was warmed up to 0° C., stirred for 35 minutes and then saturated aqueous NH4Cl was added. The mixture was warmed to room temperature, H2O was added and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts washed with brine, dried over Na2SO4, evaporated in vacuo and chromatographed (10% MeOH in CH2Cl2) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.21 (br. s., 1H), 7.75 (d, J=8.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 2H), 7.36-7.46 (m, 3H), 7.27-7.32 (m, 2H), 6.33 (br. s., 2H), 4.31 (br. s., 2H), 4.07 (s, 3H), 3.44-3.56 (m, 6H); MS (ESI) [M+H]+

Workup

  1. stirringstirred for 35 minutes
  2. temperatureThe mixture was warmed to room temperature
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc
  5. washthe combined organic extracts washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customchromatographed (10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9920c6e7342d4ec7a28e08bdae460293
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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