6-HYDRAZINONICOTINIC ACID

6-Chloronicotinic acid (0.30 g; 1.9 mmol) was added to a64percent hydrazine monohydrate solution (2 mL, 26 mmol) andplaced at 100°C for 4h. Thereafter, the reaction mixtureturned brown and was concentrated to dryness. The residuewas dissolved in water and pH adjusted to 5.5 with concentratedHCl. A precipitate was formed, filtered and washedwith ethanol, then ether to give a yellow solid (0.346 g, 96percent). Mp = 292-293°C. IR (ATR, cm-1) 3210; 3058; 3039;1696; 1636; 1613; 1536-1444; 1170; 757; 736. 1H NMR(DMSO-d6) 8.63 (s, 1H); 8.07 (d, 1H, J= 9 Hz); 6.94 (d, 1H, J = 9 Hz). 13C NMR (DMSO-d6) 167.2; 159.61;140.9; 119.9; 110.6. HRMS (ESI+) [M]+: 153.0531 observed, 153.0538 Calcd for C6H7N3O2.Example 72: 3-oxo-2, 3-dihydro-[l, 2, 4]triazolo[4, 3-a]pyridine-6-carbonyl chloride; [0235] To a solution of 6-chloronicotinic acid (20 g, 127 mmol) in 200 mL of EtOH was added hydrazine hydrate (14.8 mL, 317 mmol). The mixture was refluxed overnight, then cooled to room temperature to give a solid, which was collected by filtration, washed with petroleum ether/EA (2: 1) to give 18 g of 6-hydrazinylnicotinic acid as a yellow solid (Yield: 91percent). A mixture of 6-chloronicotinic acid (10.0 g, 63.4 mmol), hydrazine (20 mL), and water (20 mL) was refluxed at 95-100 °C for 4 h. The mixture was concentrated under vacuum and the residue was dissolved in 40 mL water. The resulting solution was acidified with 1N HCl to reach a pH 5-5.5. The solution was kept in a refrigerator overnight. The precipitated solid was collected by filtration, washed with cold water (10 mL x 2) and ether (10 mL x 2). The solid was dried to give 8.5 g (87percent) of the title compound. ES-MS: Observed [MH]General procedure: A 0.5M solution of 2-chloropyridine-5-carboxylic acid (15 mmol) was treated with hydrazine hydrate (150 mmol, added at once) and heated at reflux for 72 h. The suspension was concentrated to dryness. The residue was dissolved in water and acidified (pH = 3) with acetic acid. The precipitate of 2-hydrazinopyridine-5-carboxylic acid that formed in 15 min was filtered off, washed with water and air-dried. It was dissolved in the respective aliphatic carboxylic acid and the solution (0.5M) was heated at reflux for 48 h. Upon cooling to room temperature, the volatiles were removed in vacuo and the residue was triturated with 1M aqueous sodium bicarbonate. The precipitate thus formed was filtered off, washed with water and air dried. The resulting 1, 2, 4-triazolo[4, 3-a]pyridine 12 was dissolved in methanol (0.25M and was hydrogenated over Pd(OH)2 catalyst (0.1 equiv.) at 100 atm and 100 °C over 24 hours. The mixture was filtered while still hot and concentrated in vacuo. The residue was crystallized from isopropyl alcohol to provide analytically pure carboxylic acids 11a-d.Synthesis of 6-hydrazinopyridine-3-carboxylic acid Preparation 6 6-hydrazinylnicotinic acid [0147] A suspension of 6-chloronicotinic acid (30.0 g, 189 mmol) in 1, 4-dioxane (29.0 mL) was treated with hydrazine hydrate (134 mL, 1.51 mol) and heated to 90°C overnight. The mixture was cooled to ambient temperature and then in ice for 30 min. Precipitate formation was induced by etching the side of the flask and the precipitate was filtered and re-suspended in EtOH (500 mL) with vigorous stirring. The resulting suspension was filtered. The precipitate was dissolved in water (300 mL) and HC1 (6N) was added until pH = 1. The pH was then adjusted to 5 with NaOH (50percent, aq.) and the resulting suspension was stirred for lh. The solids were collected by filtration and dried in vacuum to give the title compound (16.65 g, 57.7 percent yield) as an off-white solid. Synthesis of 6-hydrazinylnicotinic acid To a solution of 6-chloronicotinic acid (5g, 32 mmol)) in EtOll (50 mL) was added hydrazine hydrate (3.7 mL, 80 mmol). The mixture was heated to reflux with stirring for 48 hrs. The mixture was allowed to cooled to r.t. to give a gray precipitatewhich was collected by filtration and then washed with EtCH and petroleum ether/EtOAc (2:1) to give 2 g solid (40percent)

Molecular Weight:153.14
XLogP3:-2.3
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:153.053826475
Monoisotopic Mass:153.053826475
Topological Polar Surface Area:88.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes