Methyl iodide → Methyl 3-methyl-6-[(1-methylethyl)thio]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245190Notes

Reaction equation

HRID 245190 reaction equation
[H-].[Na+].F[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[C:9]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=1)[C:8]([CH3:26])=[C:7]2[C:27]([OH:29])=[O:28].[CH3:30][CH:31]([S-:33])[CH3:32].[Na+].I[CH3:36]>CS(C)=O.O>[CH3:26][C:8]1[C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:24])([F:23])[F:25])[CH:17]=2)=[N:10][C:11]2[C:6]([C:7]=1[C:27]([O:29][CH3:36])=[O:28])=[CH:5][C:4]([S:33][CH:31]([CH3:32])[CH3:30])=[C:13]([O:14][CH3:15])[CH:12]=2

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 3470666Sodium 2-propanethiolate2×HCID 673840026-Fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 67383440Methyl 3-methyl-6-[(1-methylethyl)thio]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Sodium hydride (1.265 g, 31.6 mmol) was added to a suspension of 6-fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (8.0 g, 21.09 mmol) in dimethyl sulfoxide (50 mL), and the mixture was stirred for 20 min. Sodium 2-propanethiolate (2.53 g, 23.20 mmol) was added, and the resulting mixture was stirred at 100° C. overnight. The mixture was cooled to room temperature, treated with NaH (1.27 g of 60% dispersion in mineral oil, 31.6 mmol) and sodium 2-propanethiolate (2.53 g, 23.20 mmol), and heated at 100° C. for an additional 4 hours. The reaction mixture was cooled to room temperature. Iodomethane (3.96 mL, 63.3 mmol) was added, and the mixture was stirred for 2 hours. The mixture was diluted with water and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via column chromatography (ISCO, 330 g silica, 0-10% ethyl acetate/methylene chloride) to afford methyl 3-methyl-6-[(1-methylethyl)thio]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (5.5 g, 58% yield). This material was used in the next step without further purification. MS (m/z) 450.1 (M+H+).

Workup

  1. stirringthe resulting mixture was stirred at 100° C. overnight
  2. temperatureheated at 100° C. for an additional 4 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringthe mixture was stirred for 2 hours
  5. extractionextracted with methylene chloride (three times)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified via column chromatography (ISCO, 330 g silica, 0-10% ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-73a1ba9ac68c4cb980431d3e058346ae
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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