Diisopropylethylamine → 5-chloro-4-(5-chloro-6-cyclopropylpyridin-3-yloxy)-N-(cyclopropylsulfonyl)-2-fluorobenzamide

5-chloro-4-(5-chloro-6-cyclopropylpyridin-3-yloxy)-2-fluorobenzoic acid (Preparation 265, 15 mg, 0.44 mmol), 4-dimethylaminopyridine (81 mg, 0.66 mmol), and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (127 mg, 0.66 mmol) were suspended in dichloromethane (2.5 mL). The reaction mixture was stirred for 20 minutes then dimethyl formamide (4 mL) was added and the suspension was stirred for 10 minutes. Cyclopropanesulfonamide (107 mg, 0.88 mmol) and N,N-diisopropylethylamine (160 μL, 0.88 mmol) were added and the reaction mixture was stirred for 18 hours at room temperature. The crude reaction mixture was purified by semi-preparative reverse phase HPLC (Column phenomenex Luna C18 150×21.2 mm 110 A 5μ, 3 injections of 2 ml, detection at 254 nm, fractions of 5 ml each, Gradient Solvent A: 0.05% HCO2H in acetonitrile, Solvent B: 0.05% HCO2H in water; 0 min 10% A, 2.5 min 10% A, 32.5 min 95% A, 37.5 min 95% A then return to initial conditions, flow rate 15 ml/min) to afford the title compound as a white solid (43 mg, 22%).

1. stirringthe suspension was stirred for 10 minutes
2. stirringthe reaction mixture was stirred for 18 hours at room temperature
3. customThe crude reaction mixture
4. customwas purified by semi-preparative reverse phase HPLC (Column phenomenex Luna C18 150×21.2 mm 110 A 5μ, 3 injections of 2 ml, detection at 254 nm, fractions of 5 ml each, Gradient Solvent A
5. custom0 min 10% A, 2.5 min 10% A, 32.5 min 95% A, 37.5 min 95% A

ORD record

ord-b176c18b7ec14eaf99e3df552aaf0c45

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592629B2