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 기록

ord-da91451270474b23a55e3bf743aaa063

출처 데이터셋

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08519135B2