Oxalyl chloride → 1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide

HRID 383751Notes

Reaction equation

HRID 383751 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:16])([F:15])[F:14])=[C:5]([CH3:17])[C:4]([C:18]([OH:20])=O)=[CH:3]1.C(Cl)(=O)C(Cl)=O.[CH3:27][S:28]([C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1)(=[O:30])=[O:29].CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1>[CH3:27][S:28]([C:31]1[CH:37]=[CH:36][C:34]([NH:35][C:18]([C:4]2[C:5]([CH3:17])=[C:6]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:13]([F:16])([F:14])[F:15])[N:2]([CH3:1])[CH:3]=2)=[O:20])=[CH:33][CH:32]=1)(=[O:29])=[O:30]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 796174-(Methylsulfonyl)anilineHCID 81531DiisopropylethylamineHCID 67252161HCID 67252161, compound

Product 1

HCID 250520241,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amideYield 28%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (56 mg, 0.20 mmol) in DCM (4 mL) was added oxalyl chloride (22 pt, 0.25 mmol). After stirring 30 min, solvent was removed in vacuo to give an oil, which was re-dissolved in anhyd THF (4 mL). To this solution were added 4-methanesulfonyl-aniline (68 mg, 0.40 mmol) and DIEA (140 μL, 0.8 mmol) and the mixture was stirred at 60° C. overnight. After cooling, solvent was removed in vacuo to give a crude residue, which was purified by column chromatography on silica gel, eluted with EtOAc-hexane (0:100 to 25:75) to give the title compound (24 mg, 28%). 1H-NMR (CDCl3): δ 7.89-7.91 (m, 2H), 7.80 (m, 3H), 7.57-7.66 (m, 3H), 7.33 (d, 1H), 7.30 (s, 1H), 3.32 (s, 3H), 3.05 (s, 3H), 2.12 (s, 3H). MS (ES): 437 (MH+). E. In a manner similar to that described for Example 16D, the following compounds were prepared from the appropriate anilines:

Workup

  1. customsolvent was removed in vacuo
  2. customto give an oil, which
  3. stirringthe mixture was stirred at 60° C. overnight
  4. temperatureAfter cooling
  5. customsolvent was removed in vacuo
  6. customto give a crude residue, which
  7. customwas purified by column chromatography on silica gel
  8. washeluted with EtOAc-hexane (0:100 to 25:75)

Sources & evidence

ORD record
ord-b32b29c02dbc4c53a8b8c890aceac7ea
Source dataset
uspto-grants-2013_02
Patent number
US08367667B2

Reaction notes

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