N-Methylbutylamine → 5-n-Butyl-2-[5-(N-n-butyl-N-methylcarbamoyl)-2-chlorophenyl]-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Participants

Reaction Conditions

Reaction Steps

A solution of 40 mg (0.0589 mmole) of 5-n-butyl-2-(5-carboxy-2-chlorophenyl)-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step A) and 51.3 μL (38.1 mg, 0.295 mmole) of N,N-diisopropylethylamine in 1 mL of CH2Cl2 and 0.3 μL of DMF was stirred at 0° C. under protection from moisture as 27.9 mL (20.5 mg, 0.236 mmole) of N-methylbutylamine was added, followed by 52.1 mg (0.118 mmole) of BOP reagent. The solution was stirred at 0° C. overnight and then concentrated. The residue was reconcentrated twice from toluene. It was then taken up in CH2Cl2 and washed successively twice with 5% citric acid (aqueous), twice with 5% NaHCO3 (aqueous), and then with brine. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was flash chromatographed on silica gel (gradient elution with 1-5% MeOH in CH2Cl2) and then further purified by HPLC on a semi-preparative Zorbax C8 reverse phase column (elution with 60:40 acetonitrile-H2O) to give a 36% yield of the title compound as a colorless, glassy solid, mp >90° C. (gradual); mass spectrum (FAB) m/e 748 (M+1)+. By NMR the material appeared to exist as a mixture of amide rotamers in a ratio of approximately 1:1.

Provenance & Evidence