1-Methyl-1H-1,2,3-triazole → (4-Chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 926597Notes

Reaction equation

HRID 926597 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[N:8]1.[Cl:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH:23]([C:25]3[N:29]([CH3:30])[C:28]([CH3:31])=[N:27][CH:26]=3)[OH:24])[CH:21]=2)[N:16]=[C:15]([O:32][CH3:33])[C:14]=1[CH2:34][C:35]1[CH:36]=[N:37][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:40]=1>C1COCC1>[Cl:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]([C:25]3[N:29]([CH3:30])[C:28]([CH3:31])=[N:27][CH:26]=3)([C:11]3[N:7]([CH3:6])[N:8]=[N:9][CH:10]=3)[OH:24])[CH:21]=2)[N:16]=[C:15]([O:32][CH3:33])[C:14]=1[CH2:34][C:35]1[CH:36]=[N:37][C:38]([C:41]([F:42])([F:43])[F:44])=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 1401191-Methyl-1H-1,2,3-triazoleHCID 118005815(4-Chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol2×HCID 178418339Butyllithium

Product 1

HCID 118006216(4-Chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-BuLi (2.5 M in hexanes, 1.25 mL, 3.12 mmol) was added dropwise by syringe to a solution of 1-methyl-1H-1,2,3-triazole (268 mg, 3.22 mmol) in dry THF (32 mL) in a dry ice-methanol bath. The suspension was stirred for 30 minutes, slowly allowing the reaction mixture to warm to −10° C. (4-Chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone (0.500 g, 1.05 mmol, Intermediate 45: step f) in dry THF (5 mL) was added to the mixture via syringe and the resulting mixture was allowed to warm to ambient temperature overnight. The reaction was quenched with water. Brine was added and the aqueous mixture was extracted with ethyl acetate. The combined organic layers were dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-8% MeOH-DCM) to provide the title compound. 1H NMR (500 MHz, CDCl3) δ 8.69 (d, J=1.7 Hz, 1H), 8.24 (d, J=1.9 Hz, 1H), 8.22 (s, 1H), 7.79-7.76 (m, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.57 (d, J=8.1 Hz, 1H), 7.42 (dd, J=8.7, 2.0 Hz, 1H), 6.97 (s, 1H), 5.95 (s, 1H), 4.30 (s, 2H), 4.08 (s, 3H), 3.88 (s, 3H), 3.33 (s, 3H), 2.12 (s, 3H); MS m/e 557.8 [M+H]+.

Workup

  1. additionwas added to the mixture via syringe
  2. customThe reaction was quenched with water
  3. additionBrine was added
  4. extractionthe aqueous mixture was extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography (silica gel, 0-8% MeOH-DCM)

Sources & evidence

ORD record
ord-41b198c592da4d1b95788f46a5ff3515
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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