5-bromo-1,2-dimethyl-1H-imidazole → HCID 118006084, compound

HRID 926607Notes

Reaction equation

HRID 926607 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]([C:25]([C:27]3[N:31]([CH3:32])[C:30]([CH3:33])=[N:29][CH:28]=3)=[O:26])[CH:23]=2)[N:18]=[C:17]([O:34][CH3:35])[C:16]=1[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=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]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 72048795-bromo-1,2-dimethyl-1H-imidazoleHCID 118006351HCID 118006351, compound2×HCID 178418339Butyllithium

Product 1

HCID 118006084HCID 118006084, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-BuLi (2.5 M in hexanes, 0.24 mL, 0.6 mmol) was added dropwise by syringe to a solution of 5-bromo-1,2-dimethyl-1H-imidazole (107.8 mg, 0.616 mmol) in dry THF (6 mL) in a dry ice-acetone bath. After 1-2 minutes, (4-chloro-3-(4-fluorobenzyl)-2-methoxyquinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone (0.217 g, 0.512 mmol, Intermediate 46: step b) in dry THF (2 mL) was added to the mixture via syringe. After 5 minutes, the reaction was removed from the cold bath and was allowed to warm to ambient temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride. Water was added and the aqueous mixture was extracted with dichloromethane. The combined organic layers were dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (silica gel, 0-10% MeOH-DCM) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J=2.2 Hz, 1H), 7.63 (d, J=8.7 Hz, 1H), 7.37 (dd, J=8.8, 2.1 Hz, 1H), 7.30-7.25 (m, 2H), 6.97-6.92 (m, 2H), 6.19 (s, 1H), 6.12 (s, 2H), 4.22 (s, 2H), 4.07 (s, 3H), 3.37 (s, 6H), 2.24 (s, 6H); MS m/e 520.2 [M+H]+.

Workup

  1. waitAfter 5 minutes
  2. customthe reaction was removed from the cold bath
  3. customThe reaction was quenched with saturated aqueous ammonium chloride
  4. additionWater was added
  5. extractionthe aqueous mixture was extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by flash column chromatography (silica gel, 0-10% MeOH-DCM)

Sources & evidence

ORD record
ord-31a57f342ce04275af24057c616c72db
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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