Triethylamine → 5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid 2-(isopropylamino)pyridylamide

HRID 1438500Notes

Reaction equation

HRID 1438500 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](O)=[O:9])=[N:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.C([N:37](CC)CC)C.[CH:42]([NH:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=1)([CH3:44])[CH3:43]>C(Cl)Cl>[CH:42]([NH:45][C:46]1[C:51]([NH:37][C:8]([C:5]2[C:4]([N:11]([S:15]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([C:25]([F:27])([F:26])[F:28])[CH:19]=3)(=[O:17])=[O:16])[CH2:12][O:13][CH3:14])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)=[O:9])=[CH:50][CH:49]=[CH:48][N:47]=1)([CH3:44])[CH3:43]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2366450N-(propan-2-yl)pyridin-2-amineHCID 579422305-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid

Product 1

HCID 666489195-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid 2-(isopropylamino)pyridylamide

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 (0.5 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 2-(isopropylamino)pyridine (136 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 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 2-(isopropylamino)pyridylamide. MS m/z 577.1 (M+H).

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-6de9cd4c55c94ea0ba3ad9f27e4c59ab
Source dataset
uspto-grants-2009_11
Patent number
US07622583B2

Reaction notes

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