1,2-Dichloroethane → 6-Hydroxynicotinamide

To a solution of 6-hydroxynicotinic acid (0.049 g, 0.35 mmoles) in DMF (2.7 mL) was added EDC (0.083 g, 0.43 mmoles), HOBT (0.056 g, 0.41 mmoles) and N1-(1H-Benzimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine (0.1 g, 0.29 mmoles) and the reaction stirred overnight at room temperature. Ethyl acetate (40 mL) and water (25 mL) were added and the organic layer was washed with brine (30 mL) and saturated aqueous NaHCO3 (30 mL). The aqueous layers were extracted with ethyl acetate (3×30 mL) and the combined organic extracts dried with Na2SO4 and concentrated. The crude product was purified by radial chromatography on silica gel (1 mm plate, 2% MeOH/1% NH4OH/CH2Cl2, then 10% MeOH/1% NH4OH/CH2Cl2) to give N-{4-[1H-benzolimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amino]-butyl}-6-hydroxynicotinamide as an offwhite foam (30 mg, 16%).

1. washthe organic layer was washed with brine (30 mL) and saturated aqueous NaHCO3 (30 mL)
2. extractionThe aqueous layers were extracted with ethyl acetate (3×30 mL)
3. dry with materialthe combined organic extracts dried with Na2SO4
4. concentrationconcentrated
5. customThe crude product was purified by radial chromatography on silica gel (1 mm plate, 2% MeOH/1% NH4OH/CH2Cl2

ORD record

ord-3d07306320c5498cb43c985df89220f8

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778967B2