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

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).

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)

ORDレコード

ord-e7602e9aeb9a448c96e7f59b42fd3d45

出典データセット

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08093247B2