(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol → HCID 118006161, compound

HRID 926609Notes

Reaction equation

HRID 926609 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]([CH:48]2[CH2:53][CH2:52][N:51]([C:54](=[O:56])[CH3:55])[CH2:50][CH2:49]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]([OH:47])([C:45]3[N:41]([CH3:40])[N:42]=[N:43][CH:44]=3)[CH:48]3[CH2:53][CH2:52][N:51]([C:54](=[O:56])[CH3:55])[CH2:50][CH2:49]3)[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 118006205HCID 118006205, compound2×HCID 178418339Butyllithium

Product 1

HCID 118006161HCID 118006161, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-BuLi (2.5 M in THF, 0.60 mL, 1.5 mmol) was added dropwise over a 3 minute period to a mixture of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (0.5 g, 1.16 mmol, Intermediate 12: step d) and 1-(4-(1-methyl-1H-1,2,3-triazole-5-carbonyl)piperidin-1-yl)ethanone (0.27 g, 1.16 mmol, Intermediate 52: step b) in dry THF (8 mL) at −78° C. Stirring was continued at −78° C. for 10 minutes. The reaction mixture was then immersed in an ice bath and stirred at 0° C. for 1 hour. The reaction was then quenched with saturated aqueous NaHCO3, diluted with water and extracted with EtOAc (2×). The EtOAc extracts were dried over Na2SO4, filtered, evaporated in vacuo and purified by FCC (0-10% MeOH in DCM, gradient) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 2H), 7.80 (d, J=8.6 Hz, 1H), 7.64 (d, J=8.1 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 6.25 (s, 1H), 4.41-4.57 (m, 0.5H), 4.34 (s, 2.5H), 4.01 (s, 3H), 3.67-3.94 (m, 0.5H), 3.63 (d, J=3.5 Hz, 3H), 3.08-3.23 (m, 0.5H), 2.82-2.96 (m, 0.5H), 2.56-2.74 (m, 1.5H), 2.27-2.44 (m, 0.5H), 1.84-2.05 (m, 4H), 1.65-1.84 (m, 0.5H), 0.76-1.38 (m, 3H); MS (ESI) 588.

Workup

  1. customThe reaction mixture was then immersed in an ice bath
  2. stirringstirred at 0° C. for 1 hour
  3. customThe reaction was then quenched with saturated aqueous NaHCO3
  4. additiondiluted with water
  5. extractionextracted with EtOAc (2×)
  6. dry with materialThe EtOAc extracts were dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. custompurified by FCC (0-10% MeOH in DCM, gradient)

Sources & evidence

ORD record
ord-dea378d433ac4798bb0a3b4851c06897
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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