Aniline → 5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carboxylic acid phenylamide

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 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 aniline (93 mg, 1.00 mmol) in methylene chloride (2 mL). The reaction mixture was stirred 1 h (the reaction was monitored by LCMS), quenched with saturated aqueous NH4Cl (50 mL), and the aqueous layer was extracted with EtOAc (3×75 mL). The combined extracts were washed with 0.5 M HCl (50 mL) and 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 phenylamide. MS m/z 556.1 (M+Na); 502.1 (M+H-MeOH).

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

ORD-Eintrag

ord-b3826bede0954027ab717e8ac073e63b

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08093247B2