Triethylamine → 5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid N-methyl-N-(4-fluorophenyl)amide

HRID 1898062Notes

Reaction equation

HRID 1898062 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:11]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([C:25]([F:28])([F:27])[F:26])[CH:19]=2)(=[O:17])=[O:16])[CH2:12][O:13][CH3:14])[C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[CH3:42][N:43]([C:50]1[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=1)C1C=CC=CC=1>C(Cl)Cl>[CH3:42][N:43]([C:50]1[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=1)[C:8]([C:5]1[C:4]([N:11]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([C:25]([F:27])([F:28])[F:26])[CH:19]=2)(=[O:17])=[O:16])[CH2:12][O:13][CH3:14])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=1)=[O:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 54288754HCID 54288754, compoundHCID 579422305-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid

Product 1

HCID 579426005-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid N-methyl-N-(4-fluorophenyl)amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a magnetically stirred solution of 5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid (458 mg, 1.00 mmol) in anhydrous methylene chloride (5 mL) was added oxalyl chloride (1.0 mL) at room temperature. The reaction was heated at reflux for 1 h then was concentrated to dryness. The residue was dissolved in methylene chloride (4 mL) and this solution was added dropwise to a magnetically stirred solution of triethylamine (1.0 mL) and N-methyl-N-(4-fluorophenyl)aniline (0.50 mL, 3.5 mmol) in methylene chloride (2 mL). The reaction mixture was stirred 1 h (the reaction was monitored by LCMS) then quenched with saturated aqueous NH4Cl (50 mL), and extracted with EtOAc (3×75 mL). The combined extracts were washed with 0.5M HCl (50 mL), washed with water (50 mL), dried (MgSO4), filtered and concentrated. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate-hexane (0:100 to 100:0) to afford pure 5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid N-methyl-N-(4-fluorophenyl)amide. MS m/z 570.1 (M+Na); 526.0 (M+H−MeOH).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 1 h
  3. concentrationthen was concentrated to dryness
  4. dissolutionThe residue was dissolved in methylene chloride (4 mL)
  5. customthen quenched with saturated aqueous NH4Cl (50 mL)
  6. extractionextracted with EtOAc (3×75 mL)
  7. washThe combined extracts were washed with 0.5M HCl (50 mL)
  8. washwashed with water (50 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel using a gradient of ethyl acetate-hexane (0:100 to 100:0)

Sources & evidence

ORD record
ord-da91451270474b23a55e3bf743aaa063
Source dataset
uspto-grants-2013_08
Patent number
US08519135B2

Reaction notes

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