6-Methoxynicotinic acid

6-Methoxy-pyridine-3-carboxylic acid is an aromatic carboxylic acid and a member of pyridines.

NaOH (0.36 g, 9.0 mmol) was dissolved in MeOH (5 itiL)' and water (5 mL) . Methyl 6-methoxynicotinate (1.0Og, 5.98 mmol) was added and the mixture was stirred at 701) 1) A reaction mixture of 6-metoxynicotinonitrile (4g, 29.8mmol) in 60ml of MeOH and 5M NaOH (60ml, 300mmol) was stirred overnight at 10OB) 10 g of this product was added to sodium methanolate (obtained from 1.61 g sodium and 100 ml dried methanol). The mixture was heated under reflux for 3 hours and allowed to stand at room temperature overnight. Aqueous potassium hydroxide (10 g in 30 ml water) was added and the mixture was heated under reflux for 8 hours. It was left to stand overnight at room temperature, evaporated and the residue added to water (120 ml). The mixture was acidified to pH 3 with hydrochloric acid. The precipitate was filtered and dried to give 6-methoxynicotinic acid, m.p. 175-177.The following specific compounds of the formula (XX) may be mentioned: 6-Methoxynicotinic acid, 6-(2-Methoxyethoxy)nicotinic acid, 6-(2-Ethoxyethoxy)nicotonic acid.General procedure: To a solution of the Rl-carboxylic acids (1.1 eq.) in anhydrous DMF (2 ml) and DIPEA (1.5 eq., 103 pL, 0.59 mmol) was added HATU (1.2 eq., 180 mg, 0.47 mmol) and the reac tion mixture stirred for 30 minutes at rt. The amines 6-[4-(4-aminophenyl)piperazin-l-yl]pyr- idine-3-carbonitrile (110 mg, 0.39 mmol) or 4-(4-(4-aminophenyl)piperazin-l-yl)benzonitrile (110 mg, 0.4 mmol) were then added in DMF (2 ml) and the reaction was stirred at rt over night. H20 was then added and the resulting precipitate collected by filtration. The precipitate was washed with H20 and dried. The crude solid was dissolved in DCM/MeOH (2:1), ad sorbed onto HM-N beads (Biotage) and evaporated. The resulting material was dry-loaded onto a silica column and purified by flash column chromatography eluting with 0.5 to 3% MeOH/DCM to afford the title compounds as yellow solids.Yield: 19 mg. NMR (400 MHz, DMSO): d 10.08 (s, 1H), 8.78 (d, J=2.l Hz, 1H), 8.23 (dd, J=2.5, 8.7 Hz, 1H), 7.63 (dd, J=2.4, 9.1 Hz, 4H), 7.11 (d, J=9.2 Hz, 2H), 7.02 (d, J=9.2 Hz, 2H), 6.96 (d, J=8.7 Hz, 1H), 3.95 (s, 3H), 3.52 (dd, J=5.l, 5.1 Hz, 4H), 3.26 (dd, J=5.l, 5.1 Hz, 4H). LC-MS: Rt = 3.33 min, m/z = 414 [M+H]+.

2-Methoxy-5-pyridinecarboxylic Acidis used in the synthesis of caudatin derivatives as anti-hepatitis B virus agents. In addition it can be used the synthesize potent, selective GSK-3 inhibitors for the use in the treatment of various ailments.

Molecular Weight:153.14
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:153.042593085
Monoisotopic Mass:153.042593085
Topological Polar Surface Area:59.4
Heavy Atom Count:11
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes