(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol → HCID 118006145, compound

HRID 926610Notes

Reaction equation

HRID 926610 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[CH:49]=[N:50][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:52][CH:53]=2)=[O:47])=[CH:44][N:43]=[N:42]1>C1COCC1>[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])[N:42]=[N:43][CH:44]=3)([C:48]3[CH:49]=[N:50][C:51]([C:54]([F:55])([F:57])[F:56])=[CH:52][CH:53]=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

5

Reactant 3

HCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol2×HCID 118006241HCID 118006241, compound2×HCID 178418339Butyllithium

Product 1

HCID 118006145HCID 118006145, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of n-BuLi (2.5 M in hexanes, 1.85 mL, 4.62 mmol) was added dropwise by syringe to a mixture of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (0.31 g, 0.72 mmol, Intermediate 12: step d) and (1-methyl-1H-1,2,3-triazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (0.29 g, 1.16 mmol, Intermediate 53: step b) in dry THF (8 mL) at −78° C. over a three minute period. The mixture was stirred at −78° C. for 10 minutes then was immersed in an ice H2O bath and stirred at 0° C. for 1 hour. The solution was quenched with saturated aqueous NaHCO3, warmed to room temperature, and the layers were separated. The aqueous layer was further extracted with EtOAc and the organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by FCC [(30% EtOH in EtOAc)/heptane, gradient] to provide the title compound. MS (ESI) 608 [M+H]+.

Workup

  1. customthen was immersed in an ice H2O bath
  2. stirringstirred at 0° C. for 1 hour
  3. customThe solution was quenched with saturated aqueous NaHCO3
  4. temperaturewarmed to room temperature
  5. customthe layers were separated
  6. extractionThe aqueous layer was further extracted with EtOAc
  7. washthe organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was purified by FCC [(30% EtOH in EtOAc)/heptane, gradient]

Sources & evidence

ORD record
ord-45ccdee29b65461e9891c2de57d25167
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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