1-Methylimidazole → (3-Benzyl-2,4-dimethylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

HRID 928767Notes

Reaction equation

HRID 928767 reaction equation
I[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C([Mg]Cl)(C)C.[CH2:13]([C:20]1[C:21]([CH3:37])=[N:22][C:23]2[C:28]([C:29]=1[CH3:30])=[CH:27][C:26]([C:31](N(OC)C)=[O:32])=[CH:25][CH:24]=2)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CN1C=CN=C1>C1COCC1>[CH2:13]([C:20]1[C:21]([CH3:37])=[N:22][C:23]2[C:28]([C:29]=1[CH3:30])=[CH:27][C:26]([C:31]([C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1)=[O:32])=[CH:25][CH:24]=2)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 12776685-Iodo-1-methyl-1H-imidazoleHCID 867156093-Benzyl-N-methoxy-N,2,4-trimethylquinoline-6-carboxamide2×HCID 178418918HCID 178418918, compound

Product 1

HCID 86715610(3-Benzyl-2,4-dimethylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A translucent solution of 5-iodo-1-methyl-1H-imidazole (197 mg, 0.946 mmol) in THF (1.5 mL) was stirred at 0° C. while iPrMgCl (2.01 M in THF, 0.43 mL, 0.864 mmol) was added dropwise under argon. The ice bath was immediately removed and the white mixture was stirred at room temperature for 15 minutes, and was then added rapidly dropwise to a solution of 3-benzyl-N-methoxy-N,2,4-trimethylquinoline-6-carboxamide (71.9 mg, 0.215 mmol, Intermediate 34: step c) in THF (0.5 mL) at room temperature. The resulting milky opaque mixture was stirred at room temperature for 1.5 hours, and was then quenched with 1 M aqueous NaHCO3 (6 mL) and extracted with EtOAc (2×6 mL). The combined organic layers were shown by LCMS to be a mixture of title compound and starting material, so the material was concentrated from THF (3×) and re-subjected to the above conditions but with reaction at 50° C. for 2 hours. The reaction was then worked up as described above, and the residue was flash chromatographed with a heptane to 100% EtOAc gradient to provide a 1:4 mol ratio of the title compound and N-methylimidazole.

Workup

  1. additionwas added dropwise under argon
  2. customThe ice bath was immediately removed
  3. stirringThe resulting milky opaque mixture was stirred at room temperature for 1.5 hours
  4. customwas then quenched with 1 M aqueous NaHCO3 (6 mL)
  5. extractionextracted with EtOAc (2×6 mL)
  6. additiona mixture of title compound
  7. concentrationso the material was concentrated from THF (3×)
  8. customre-subjected to the above conditions but with reaction at 50° C. for 2 hours
  9. customchromatographed with a heptane to 100% EtOAc gradient
  10. customto provide a 1

Sources & evidence

ORD record
ord-2498079e5cae414886cdaeca76bcd7ff
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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