Methyl iodide → HCID 70665114, compound

HRID 1403563Notes

Reaction equation

HRID 1403563 reaction equation
[C:1]1([CH3:29])[C:2]([NH:7][C:8]2[C:9]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[N:10][C:11]3[C:16]([N:17]=2)=[CH:15][C:14]([C:18]([O:20]C)=[O:19])=[CH:13][CH:12]=3)=[CH:3][CH:4]=[CH:5][CH:6]=1.[H-].[Na+].[CH3:32]I>O1CCCC1>[F:28][C:25]1[CH:24]=[CH:23][C:22]([C:9]2[C:8]([N:7]([CH3:32])[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=3[CH3:29])=[N:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:18]([OH:20])=[O:19])[CH:15]=3)[N:10]=2)=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 70664909HCID 70664909, compound

Product 1

HCID 70665114HCID 70665114, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 3-(o-toluidino)-2-(4-fluorophenyl)quinoxaline-6-carboxylate (145 mg, 0.37 mmol) in tetrahydrofuran (30 mL) was added sodium hydride (74.9 mg, 3.12 mmol) at 0° C. with stirring for 30 min, followed by the addition of CH3I (1.5 mL) dropwise. The reaction mixture was stirred overnight at room temperature. The reaction was then quenched with water (50 mL), adjusted to pH 5 with HCl (3N), and extracted with ethyl acetate (3×80 mL). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the residue, which was purified by Prep-HPLC under the following conditions [(Agilent 1200 prep HPLC): Column, SunFire Prep C18, 19*50 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (25% CH3CN up to 67% in 10 min); Detector, UV 220 nm] to afford 2-(4-fluorophenyl)-3-(methyl(o-tolyl)amino)quinoxaline-6-carboxylic acid as a light yellow solid (46.5 mg, 30%).

Workup

  1. stirringThe reaction mixture was stirred overnight at room temperature
  2. customThe reaction was then quenched with water (50 mL)
  3. extractionextracted with ethyl acetate (3×80 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give the residue, which
  7. customwas purified by Prep-HPLC under the following conditions [(Agilent 1200 prep HPLC)
  8. waitmobile phase, water with 0.05% TFA and CH3CN (25% CH3CN up to 67% in 10 min)

Sources & evidence

ORD record
ord-9bee5685d8544891aa23ed8134116d21
Source dataset
uspto-grants-2014_12
Patent number
US08912188B2

Reaction notes

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