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

HRID 419051Notes

Reaction equation

HRID 419051 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.[CH:42]([NH:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)([CH3:44])[CH3:43]>C(Cl)Cl>[CH:42]([N:45]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=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:26])([F:27])[F:28])[CH:19]=2)(=[O:16])=[O:17])[CH2:12][O:13][CH3:14])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=1)=[O:10])([CH3:44])[CH3:43]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 13032N-IsopropylanilineHCID 65578Oxalyl chlorideHCID 579422305-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid

Product 1

HCID 579425495-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid N-isopropyl-N-phenylamide

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 (229 mg, 0.50 mmol) in anhydrous methylene chloride (5 mL) was added oxalyl chloride (1.0 mL) at room temperature. The reaction was heated at reflux for 2 h, then 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-isopropylaniline (135 mg, 1.00 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 the aqueous layer extracted with EtOAc (3×75 mL). The combined extracts were washed with 0.5 M 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-isopropyl-N-phenylamide. MS m/z 576.0 (M+H); 544.0 (M+H-MeOH).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 2 h
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in methylene chloride (4 mL)
  5. customthen quenched with saturated aqueous NH4Cl (50 mL)
  6. extractionthe aqueous layer extracted with EtOAc (3×75 mL)
  7. washThe combined extracts were washed with 0.5 M 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-ce7e5f14dfdb41eaaf56ae496d53f255
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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