6-chloro-4-methyl-2H-pyridazin-3-one

A solution of 6- chloro-3-methoxy-4-methylpyridazine (3.31 g, 20.9 mmol) in 4:1 dioxane: water (100 mL) was treated with 12.0 M HC1(aq) (1.91 mL, 23.0 mmol) and stirred for 60 h at 60 °C. The reaction mixture was concentrated under vacuum, and the resulting crude residue was purified by silica chromatography (1-30percent DCMIMeOH with 2percent NH4OH as the gradient eluent) to afford the title compound (2.99 g, 99percent yield). ‘HNMR(400 IVIFIz, DMSO-d6) 13.03 (s, 1H), 7.44 (s, 1H), 2.05 (s, 3H).3, 6-Dichloro-4-methylpyridazine (30.6 g, 190 mmol) was suspended in glacial AcOH (800 mL) at ambient temperature and heated in an oil bath thermostatted at 110-115 °C for 3 h. (The mixture became homogenous after 1 h.) The mixture was allowed to cool and the AcOH was removed by vacuum distillation. The resulting solid residue was slowly treated with sat. NaHCOIntermediate VII6-Chloro-4-methyl-2H-pyridazin-3-one and 6-chloro-5-methyl-2H-pyridazin-3-one A suspension of 3, 6-dichloro-4-methylpyridazine (6.60 g) in 3.3 M aqueous NaOH solution (66 mL) was stirred at reflux temperature for 2 h. The heating bath was removed and 50percent aqueous acetic acid (25 mL) was added. The aqueous solution was adjusted to pH value 6 and the precipitate formed thereafter was separated by filtration and washed with little water. The precipitate was chromatographed on silica gel (cyclohexane/ethyl acetate 90:10->0:100) to separate the two title compounds.6-Chloro-4-methyl-2H-pyridazin-3-one: Yield: 2.70 g (46percent of theory). Mass spectrum (ESI3, 6-Dichloro-4-methylpyridazine (30.6 g, 190 mmol) was suspended in glacial AcOH (800 mL) at ambient temperature and heated in an oil bath thermostatted at 110-115 C for 3 h. (The mixture became homogenous after 1 h.) The mixture was allowed to cool and the AcOH was removed by vacuum distillation. The resulting solid residue was slowly treated with sat. NaHCO3 solution (200 mL) to give a pale yellow heterogenous mixture that was adjusted to pH 6 by the slow addition of solid NaHCO3 with vigorous stirring. The mixture was extracted with dichloromethane (2 x 250 mL) and the combined organic phase was washed with sat. NaCl solution (60 mL), dried (MgSO4) and evaporated to afford a solid (20.9 g). The crude material was subjected to column chromatography (gradient 1% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2) to afford, 6-chloro-4-methyl-2H-pyridazin-3-one (13.4 g, 92.7 mmol; 49%) [Rf 0.21 (2.5% MeOH/CH2Cl2)] and 6-chloro-5-methyl-2H-pyridazin-3-one (5.00 g, 34.6 mmol; 18%) [Rf 0.11 (2.5% MeOH/CH2Cl2)] as a colourless solids. 6-Chloro-4-methyl-2H-pyridazin-3-one: 1H NMR (200 MHz, CDCl3-CD3OD): 2.12 (3H, s), 3.55 (1H, brs), 7.05 (1H, s); 13C NMR (50 MHz, CDCl3): 16.1 (CH3), 131.7 (CH-5), 139.0 (C-6), 143.0 (C-4), 161.9 (C-3). 6-Chloro-5-methyl-2H-pyridazin-3-one: mp 172-173 C (from CH2Cl2/light petrol); 1H NMR (200 MHz, CDCl3) delta 2.20 (3H, d, J = 1.3 Hz), 7.13 (1H, q, J = 1.3 Hz); 13C NMR (50 MHz, CDCl3) 16.3 (CH3), 131.9 (CH-5), 139.2 (C-4), 143.2 (C-6), 161.9 (C-3). LRMS (EI): 144 ([M+]). Anal. calcd for C5H5ClN2O: C, 41.54; H, 3.49; N, 19.38. Found: C, 41.55; H, 3.51; N, 19.22.Intermediate VII6-Chloro-4-methyl-2H-pyridazin-3-one and 6-chloro-5-methyl-2H-pyridazin-3-one A suspension of 3, 6-dichloro-4-methylpyridazine (6.60 g) in 3.3 M aqueous NaOH solution (66 mL) was stirred at reflux temperature for 2 h. The heating bath was removed and 50% aqueous acetic acid (25 mL) was added. The aqueous solution was adjusted to pH value 6 and the precipitate formed thereafter was separated by filtration and washed with little water. The precipitate was chromatographed on silica gel (cyclohexane/ethyl acetate 90:10->0:100) to separate the two title compounds.6-Chloro-4-methyl-2H-pyridazin-3-one: Yield: 2.70 g (46% of theory). Mass spectrum (ESI+): m/z=145/147 (Cl) [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta 2.06 (d, J=1.3 Hz, 3H), 7.44 (incompletely resolved q, J=1.3 Hz, 1H), 13.03 (broad s, 1H).6-Chloro-5-methyl-2H-pyridazin-3-one: Yield: 1.90 g (32% of theory). Mass spectrum (ESI+): m/z=145/147 (Cl) [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta 2.19 (d, J=1.3 Hz, 3H), 6.91 (incompletely resolved q, J=1.3 Hz, 1H), 13.02 (broad s, 1H).To a mixture containing

Molecular Weight:144.56
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:144.0090405
Monoisotopic Mass:144.0090405
Topological Polar Surface Area:41.5
Heavy Atom Count:9
Complexity:207
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes