5-(benzyloxy)-2-(hydroxyMethyl)pyridin-4-ol

A suspension of 5-(benzyloxy)-2-(hydroxymethyi)-4H-pyran-4-one(53.2 g, 229 mmol) in IMS (75 ml) and aq. NH40H solution (400 ml)was stirred at 70°C for 18 h. The cooled solution was diluted with water(400 ml), cooled to soc and the suspension stirred for 30 min. Thesolid was filtered and dried under vacuum to leave the title compound1 0 as a pale brown solid (42.5 g, 80percent yield). LC-MS (M-H+) = 232. 1 HNMR (300 MHz, DMSO-d6): o 11.08 (br s, 1 H), 7.51 - 7.28 (m, 6H), 6.16 (br s, 1 H), 5.56 (br s, 1 H), 5.01 (s, 2H), 4.34 (s, 2H).10 g of compound 3 was added to 17 mL of absolute ethanol and heated under reflux in an oil bath with stirring. Then, 83 mL of aqueous ammonia (25-28percent) was injected thereinto and reacted at 60 °C overnight. The reaction was monitored by TLC. After the reaction was completed (reaction time was 12 hours), the mixture was allowed to stand at room temperature, precipitated and precipitated by filtration, and then the precipitate was washed twice with a small amount of diethyl ether and dried to obtain product 4a. Yield 76percent.Weigh 0.129 mol (30 g) of compound 3 was added to 50 mL of a three-necked flask and then 50 mL of absolute ethanol was added, stirred under reflux with heating, followed by removal of 250 mL of aqueous ammonia (25 to 28percent by mass) and monitored by TLC System reaction process. At about 60 ° C for about 12 h, the feed is reacted completely. After the end of the reaction, the mixture was cooled to room temperature, and a precipitate was produced at the bottom of the flask. The precipitate was collected by filtration, and the crystals were crystallized three times and dried to give Compound 4a. Yield 75.6percent.To a solution of compound 2 (30 g) in absolute EtOH (50 mL) wasadded aqueous ammonia (25percent-28percent, 250 mL). The mixture was refluxed overnightuntil the reaction was completed. After the reaction mixture was cooled to theroom temperature, the precipitate was collected by filtration, washed twicewith a small amount of diethyl ether and dried, providing the product compound 3 as a white solid (22 g, 73.6percent yield).A mixture of 5-benzyloxy-2-hydroxymethyl-4H-pyran-4-one (9.7 g, 42 mmole; prepared from Kojic acid by the method of Erol, D. J. Med. Chem. 1994, 29, 893) To a stirred solution of compound 9a (5.2 g) in ethanol (15 mL), was added cone NH