4-AMINORESORCINOL HYDROCHLORIDE

(2, 4-Dihydroxyphenyl)-carbamic acid benzyl ester (KCBG02) To a cooled solution (0 C.) of 4-amino resorcinol.HCl (1.0 g, 6.18 mmol) in H2O (10 mL) was added dropwise aq. NaOH (0.49 g, 12.3 mmol) in H2O (15 mL). To this mixture were added slowly Cbz-Cl (Carbobenzoxy chloride, 1.06 mL, 7.43 mmol) and NaOH (0.25 g) in H2O (5 mL). After stirring for 1 h at room temperature, the mixture was extracted with EtOAc (2*50 mL). The organic layer was dried over MgSO4 (10 g), filtrated and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc:hexane=1:5) to give (2, 4-dihydroxyphenyl)-carbamic acid benzyl ester (KCBG02. 1.28 g, 80%). 1H-NMR (200 MHz, CDCl3): delta 8.96 (br s, 1H, OH), 8.46 (br s, 1H), 7.47 (d, 1H, NH), 7.33~7.41 (m, 5H), 6.45 (d, 1H, J=2.50), 6.33 (dd, 1H, J=8.64, 2.50), 5.17 (s, 2H).4-Aminoresorcinol HCI (620 mg, 2.8 mmol) was slurried in THF (10 ml) and triethylamine (1.6 ml, 3 eq) was added. To the stirred solution, cooled with an ice-bath, 6-chloronicotinoyl chloride (2.0 g, 3 eq) dissolved in THF (15 ml) was added dropwise. After the addition the mixture was allowed to stir for 3 days at rt. The reaction was poured out on ice and the solid was filtered. The wet solid was dissolved in THF (25 ml) and ethanol (25 ml) by heating. 2 M NaOH (20 ml) was added dropwise to the still warm solution. After 10 min the organic solvent was removed on the rotory evaporator and the mixture dissolved by adding more water. The solution was neutralized wit 6 M HCI (6 ml) and the solid was filtered to give 6-chloro-N-(2, 4-dihydroxyphenyl)pyridine-3- carboxamide (0.71 g, 71% yield, m/z (M-l) 263.1).