METHYL 2-OXO-1,2-DIHYDRO-3-PYRIDINECARBOXYLATE

To a solution of 2-hydroxynicotinic acid (3-067-01) (50 g) in methanol (500 ml) were added conc. sulfuric acid (15 mL) and toluene (100 mL) at room temperature. After the reaction mixture was stirred for 28 h attached Dienstark reflux tube and neutralized with an aqueous potassium carbonate solution, the solvent was evaporated. To the residue were added aqueous saturated ammonium chloride solution and chloroform, and the organic layer was separated, and the aqueous layer was extracted with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to give 2-hydroxynicotinic acid methyl ester (3-067-02) (46 g, 84percent) as a white solid.1H NMR (300 MHz, CDCl3): δ 3.92 (s, 3H), 6.45 (dd, J = 7.3, 6.4 Hz, 1H), 7.78 (dd, J = 6.4, 2.4 Hz, 1H), 8.29 (dd, J = 7.3, 2.4 Hz, 1H)To a solution of 2-hydroxynicotinic acid (3-067-01) (50 g) in methanol (500 ml) were added conc. sulfuric acid (15 ml) and toluene (100 mL) at room temperature. After the reaction mixture was stirred for 28 h attached Dienstark reflux tube and neutralized with an aqueous potassium carbonate solution, the solvent was evaporated. To the residue were added aqueous saturated ammonium chloride solution and chloroform, and the organic layer was separated, and the aqueous layer was extracted with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to give 2-hydroxynicotinic acid methyl ester (3-067-02) (46 g, 84percent) as a white solid.<1>H NMR (300 MHz, CDCl3): delta 3.92 (s, 3H), 6.45 (dd, J = 7.3, 6.4 Hz, 1H), 7.78 (dd, J = 6.4, 2.4 Hz, 1H), 8.29 (dd, J = 7.3, 2.4 Hz, 1H).A mixture of 1.00 g (7.20 mmol) of 2-hydroxypyridine-3-carboxylic acid and 7.20 mL of concentrated HExample 117-2 Synthesis of methyl 2-hydroxy nicotinate [0404] After 1 g (7.19 mmol) of 2-hydroxynicotinic acid was dissolved in 20 mL of methylene chloride, 3.4 g (28.8 mmol) of thionyl chloride was added thereto. Afterward, the resulting reaction solution was stirred at about 75° C. for 3 hours. After termination of the reaction was determined by liquid chromatography, the solvent was removed in vacuo. This compound was dissolved in methanol and was then stirred at room temperature for about 2 hours. The compound was extracted three times with water and dichloromethane, and an organic solvent phase was purified using column chromatography (hexane:ethyl acetate=1:1) to obtain a target compound (Actual yield: 480 mg, Percent yield: 53percent).2-hydroxy-nicotinic acid (1.763 g, 12.7 mmol) was suspended in methanol (18 ml). Thereto concentrated sulfuric acid (0.54 ml), heated to reflux overnight using a Dienstark by addition of toluene (4 ml). After the reaction was quench with aqueous potassium carbonate solution. The solvent was distilled off. Chloroform and a saturated aqueous solution of sodium bicarbonate was added, and the mixture was extracted with chloroform. Dried over magnesium sulfate, the solvent was evaporated to give the title compound 522 mg, 26.8percent) as a white solid.EXAMPLE 208A Methyl 2-hydroxynicotinate (500 mg, 3.27 mmol) and N-bromosuccinimide (756 mg, 4.25 mmol) were dissolved in dichloromethane and the mixture was stirred at 50 C for 48 hours. The mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was filtered with a small amount of dichloromethane to obtain the title compound (0.3 g, yield: 40%, yellow solid). *H NMR (500MHz, DMSO-d6) d 8.07 (d, J = 5.0 Hz, 1H), 7.98 (d, J = 5.0 Hz, 1H), 3.75 (s, 3H)

Molecular Weight:153.14
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:153.042593085
Monoisotopic Mass:153.042593085
Topological Polar Surface Area:55.4
Heavy Atom Count:11
Complexity:252
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes