(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926541Notes

Reaction equation

HRID 926541 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](C(C3C(C)=NC(C)=CC=3)O)[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=1.C([Li])CCC.[CH3:40][C:41]1[S:42][C:43]([C:47]([C:49]2[N:53]([CH3:54])[N:52]=[N:51][CH:50]=2)=[O:48])=[C:44]([CH3:46])[N:45]=1>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:47]([C:43]3[S:42][C:41]([CH3:40])=[N:45][C:44]=3[CH3:46])([C:49]3[N:53]([CH3:54])[N:52]=[N:51][CH:50]=3)[OH:48])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:27][CH:26]=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 86715632(2,4-Dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone2×HCID 178418339Butyllithium

Product 1

HCID 74221204(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (500 mg, 116 mmol, Intermediate 12: step d) was added THF (15 mL) at room temperature which resulted in a colorless homogeneous mixture. The solution was cooled to −70° C. (the solution remained homogeneous) and then n-butyllithium (2.5 M in hexanes, 0.45 mL, 1.13 mmol) was added dropwise. The color of the solution became a dark brown. After 1 minute, (2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (275 mg, 1.24 mmol in 2 mL THF, Intermediate 23: step b) was introduced and the color of the mixture went from dark brown to greenish to light orange color all within 1 minute. The mixture was allowed to warm to 0° C. over 45 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The mixture was diluted further with water and extracted with EtOAc (3×45 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to afford a light orange foam. The crude was chromatographed on silica gel (initially using 10% CH3CN-toluene then changing to 80% CH3CN-DCM) to provide the title compound as an off white solid.

Workup

  1. customresulted in a colorless homogeneous mixture
  2. additionwas added dropwise
  3. customwithin 1 minute
  4. temperatureto warm to 0° C. over 45 minutes at which time the reaction
  5. customwas quenched with aqueous NH4Cl solution
  6. additionThe mixture was diluted further with water
  7. extractionextracted with EtOAc (3×45 mL)
  8. washThe combined organics were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a light orange foam
  13. customThe crude was chromatographed on silica gel (

Sources & evidence

ORD record
ord-b7f82134fb4b4209a2fb9a9699a7fcd6
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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