5-bromo-1,2-dimethyl-1H-imidazole → HCID 118006341, compound

HRID 926598Notes

Reaction equation

HRID 926598 reaction equation
[Li]CCCC.Br[C:7]1[N:11]([CH3:12])[C:10]([CH3:13])=[N:9][CH:8]=1.[Cl:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH:25]([C:27]3[N:31]([CH3:32])[C:30]([CH3:33])=[N:29][CH:28]=3)[OH:26])[CH:23]=2)[N:18]=[C:17]([O:34][CH3:35])[C:16]=1[CH2:36][C:37]1[CH:38]=[N:39][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:41][CH:42]=1>C1COCC1>[Cl:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]([C:27]3[N:31]([CH3:32])[C:30]([CH3:33])=[N:29][CH:28]=3)([C:7]3[N:11]([CH3:12])[C:10]([CH3:13])=[N:9][CH:8]=3)[OH:26])[CH:23]=2)[N:18]=[C:17]([O:34][CH3:35])[C:16]=1[CH2:36][C:37]1[CH:38]=[N:39][C:40]([C:43]([F:44])([F:45])[F:46])=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 72048795-bromo-1,2-dimethyl-1H-imidazoleHCID 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 118006341HCID 118006341, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-BuLi (2.5 M in hexanes, 1.3 mL, 3.25 mmol) was added dropwise by syringe to a solution of 5-bromo-1,2-dimethyl-1H-imidazole (614.1 mg, 3.509 mmol) in dry THF (12 mL) in a dry ice-acetone bath. After 1-2 minutes, a solution of (4-chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone (0.830 g, 1.75 mmol, Intermediate 45: step f) in dry THF (5 mL) was added dropwise. The reaction was stirred for 5 minutes, then was removed from the cold bath and allowed to warm to ambient temperature. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was partitioned between water and dichloromethane. The separated aqueous phase was further extracted with dichloromethane. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM) followed by trituration with dichloromethane to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.74 (d, J=2.1 Hz, 1H), 8.22 (d, J=2.2 Hz, 1H), 7.79 (dd, J=8.0, 2.1 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.59 (d, J=8.1 Hz, 1H), 7.41 (dd, J=8.8, 2.1 Hz, 1H), 6.15 (s, 2H), 5.47 (s, 1H), 4.34 (s, 2H), 4.06 (s, 3H), 3.40 (s, 6H), 2.29 (s, 6H); MS m/e 571.0 [M+H]+.

Workup

  1. customwas removed from the cold bath
  2. customThe reaction was quenched with saturated aqueous ammonium chloride
  3. customThe mixture was partitioned between water and dichloromethane
  4. extractionThe separated aqueous phase was further extracted with dichloromethane
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM)

Sources & evidence

ORD record
ord-6316478eb553493fa8dd95c1d1f16359
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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