6-Chloropyridazin-3-ol

To a solution of 3, 6-dichloro-pyridazine (1g, 0.006759mol) in AcOH/H2O (5/1) (20mL) wasadded KOAc (0.662 g, 0.006759 moL), and the mixture was heated to 140 C for 70 min undermicrowave conditions. The vial was cooled and the solvent was evaporated in vacuo. EtOAc and H2Owere added. The layers were separated, and the aqueous layer was extracted with EtOAc. The combinedorganic phase was washed brine, dried over Na2SO4, and concentrated to give 6-chloro-2H-pyridazin-3-one (0.813g, 92.5percent). 1H NMR (CDCl3): 6.96 (d, 1H), 7.25 (d, 1H).General procedure: A suspension of 3, 6-dichloropyridazine (25.50 g, 171.2 mmol) in 100 mL of water was treated with NaOH (15.06 g, 376.6 mmol) and heated at 80 °C for 2 h. The resulting red solution was allowed to cool to rt and was then acidified to pH 1 with concentrated HCl (aq). The off-white solid was washed with water and EtA) 6-Chloro-2H-pyridazin-3-one: To four microwave vials were added 3, 6-dichloropyridazine (250 mg, 1.68 mmol), potassium acetate (165 mg, L68 mmol) and 5 mL acetic acid/ water (5 : 1). The reaction was heated at 140 22.47 g (150 mmoles) of 3, 6-dichloropyridazine are placed in 50 mL of acetic acid and agitated for 9h under reflux. The reaction medium is diluted in 50 mL of water and concentrated to dryness. The residue obtained is purified by silica gel flash chromatography (CH6-4-f4- (5-Chloro-lH-indole-2-sulphonyl)-piperazine-l-carbonvl]-phenyl}-2- (2-dimethylamino-ethvl)-2H-pyridazin-3-one Step A. To a microwave vial was added 3, 6-dichloropyridazine (645mg, 4.33mmol), potassium acetate (425 mg, 4.33 mmol) and 9 mL acetic acid/water (5: 1). The reaction mixture was heated at 140 °C for 70 minutes. The solvent was evaporated and the crude was purified by preparative HPLC using a gradient of acetonitrile/5 percent acetonitrile- water phase containing 0.1 M ammonium acetate, to give 436 mg of 6-chloro-2H- pyridazin-3-one (77 percent yield). 1H NMR (400 MHz ; methanol-d4 as solvent and internal reference) δ (ppm) 6.96 (d, 1H), 7.45 (d, 1H).In a 50mL round-bottom flask were added a solution of absolute ethanol (10 mL) and dichloropyridazine (1.00 g, 6.71 mmol). The mixture was stirred at reflux of ethanol for 24 h. After cooling down to room temperature, a saturated NH4Cl solution (30 mL) was added and the resulting solution was extracted with CH2Cl2 (330 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under vacuum. The crude solid was triturated in petroleum ether, filtered through a Buchner to afford the pure product (0.785 g, 90percent).Step 1: Preparation of ethyl 2-(3-chloro-6-oxo-pyridazin-l-yl) acetate To a solution of 3-chloro-lH-pyridazin-6-one (5 g, 38.3 mmol, TCI, Catalog number: C2377) in dimethylformamide (30 mL) was added potassium carbonate (17.9 g, 130.0 mmol), followed by slow addition of ethyl 2-bromoacetate (4.7 mL, 42.0 mmol) at 0 C. After the addition was completed, the reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours, then diluted by water (5 mL) and extracted with ethyl acetate (30 mL) three times. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate and concentrated under vacuum. The crude was purified by flash column chromatography (eluted with petroleum ether/ethyl acetate = 3:1) to give 7.4 g of ethyl 2-(3- chloro-6-oxo-pyridazin-l-yl) acetate as a colorless solid.

Molecular Weight:130.53
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:129.9933904
Monoisotopic Mass:129.9933904
Topological Polar Surface Area:41.5
Heavy Atom Count:8
Complexity:173
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes