5-Bromo-1-methyl-1H-imidazole → HCID 74220814, compound

HRID 928839Notes

Reaction equation

HRID 928839 reaction equation
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C([Mg]Cl)C.[CH2:12]([C:19]1[C:20]([C:42]([NH:44][CH3:45])=[O:43])=[N:21][C:22]2[C:27]([C:28]=1[C:29]([F:32])([F:31])[F:30])=[CH:26][C:25]([C:33](=[O:41])[C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)=[CH:24][CH:23]=2)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(Cl)Cl>[CH2:12]([C:19]1[C:20]([C:42]([NH:44][CH3:45])=[O:43])=[N:21][C:22]2[C:27]([C:28]=1[C:29]([F:32])([F:30])[F:31])=[CH:26][C:25]([C:33]([C:34]1[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=1)([OH:41])[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1)=[CH:24][CH:23]=2)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 86715666HCID 86715666, compound2×HCID 178461633HCID 178461633, compound

Product 1

HCID 74220814HCID 74220814, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Bromo-1-methyl-1H-imidazole (1.36 mL, 0.5 M in DCM over 3 Å molecular sieves, 0.678 mmol) was treated with EtMgCl (0.325 mL, 2.09 M in THF, 0.678 mmol) dropwise under argon with stirring at room temperature over 1 minute, and the resulting translucent/semi-opaque reaction was stirred at room temperature for 20 minutes. This was treated dropwise over 2 minutes with a solution of 3-benzyl-6-(4-fluorobenzoyl)-N-methyl-4-(trifluoromethyl)quinoline-2-carboxamide (90.4 mg, 0.194 mmol, Intermediate 35: step f) in DCM (1.2 mL) with stirring at room temperature, and the resulting orange reaction was immediately stirred at 40° C. for 13 hours. The resulting orange opaque mixture was cooled to room temperature, partitioned with 5 M aqueous NH4Cl (3 mL), and the aqueous layer was extracted with DCM (1×5 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was dry load flash chromatographed using 2:3 toluene/acetone (isocratic elution) to yield the title compound as a pale yellow foam. 1H NMR (400 MHz, CDCl3) δ ppm 8.32 (s, 1H), 7.88 (d, J=9.09 Hz, 1H), 7.69 (d, J=10.61 Hz, 1H), 7.30-7.38 (m, 3H), 7.10-7.24 (m, 4H), 6.97-7.09 (m, 4H), 6.29 (s, 1H), 4.91 (s, 2H), 3.39 (s, 3H), 2.89 (d, J=5.05 Hz, 3H); MS m/e 549.2 [M+H]+.

Workup

  1. customthe resulting translucent/semi-opaque reaction
  2. stirringwas stirred at room temperature for 20 minutes
  3. stirringwith stirring at room temperature
  4. customthe resulting orange reaction
  5. stirringwas immediately stirred at 40° C. for 13 hours
  6. temperatureThe resulting orange opaque mixture was cooled to room temperature
  7. custompartitioned with 5 M aqueous NH4Cl (3 mL)
  8. extractionthe aqueous layer was extracted with DCM (1×5 mL)
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was dry load flash
  13. customchromatographed

Sources & evidence

ORD record
ord-fbe3362eda294e44a8e98923a9038d8b
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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