5-Iodo-3(2H)-pyridazinone

4, 5-Dichloropyridazin-3(2H)-one (10 g, 60.61 mmol) was treated with 47percent hydroiodic acid (75 mL) in a sealed tube, and the reaction was heated at 150° C. for 25 h. At this point, the reaction was filtered and washed with water (100 mL). The solids were treated with water (200 mL), heated to 50° C., and sodium thiosulfate was added with stirring until the solution turned a light brown color and a precipitate formed. The resulting mixture was filtered, and the filtrate was dried in vacuo. The resulting brown solid was washed with hot ethanol (roughly 78° C., 200 mL) and filtered. The red/brown filtrate was dried in vacuo. The resulting dark brown solid was triturated with methylene chloride (20 mL), triturated with hexanes (4.x.30 mL), and dried in vacuo to afford 5-iodo-2H-pyridazin-3-one (8.640 g, 64percent) as a brown solid. The material was used without further purification.A round bottom flask charged with 4, 5-dichloro-2H-pyridazin-3-one (1, 15.0 g, 90.9 mmol) and HI (57percent in HExample 35; 5-(3-Cyclobutyl-2, 3, 4, 5-tetrahydro-lH-benzo[d]azepin-7-yloxy)-2-methyl-2H-pyridazin- 3 -one; General synthesis of Example 35:; Step 1: Synthesis of 5-iodo-2H-pyridazin-3-one.; A round-bottom flask contained 4, 5-dichloro-2H-pyridazin-3-one (10.0 g, 60.6 mmol) and hydriodic acid (57percent in HExample 404: N-(2, 2-Dimethylpropyl)-5-(4-methylpiperazin-1 -yl)pyridazin-3- amine. 5-iodopyridazin-3(2H)-one. A mixture of 4, 5-dichloropyridazin-3(2H)-one (25 g, 0.152 mol) in 250 ml_ of hydrogen iodide acid (57wpercent) was heated to reflux for 18 hrs. The solution was cooled to ambient temperature and filtered. The precipitate was washed with saturated sodium thiosulfate solution. The precipitate was dried to give the desired product as a yellow solid (Int. Pat. Appl. Publ. WO 2008/013838 (Cephalon Inc., January 31 , 2008)) (15 g, 45percent). 4, 5-Dichloropyridazin-6-one (10 g, 60.6 mmol) and 57 wt. percent hydroiodic acid in water (80 mL, 1.0 mmol) was heated to 150° C. for 24 h. The reaction was cooled to rt, the solid was washed with sodium thiosulfate. The crude product was triturated with CHA mixture of A round bottom flask charged with 4 (6.1 g, 27.6 mmol), formaldehyde (37% in H2O, 22 mL) and H2O (50 mL) was stirred at reflux for 18 h. After cooling to ambient temperature, the resulted crystalline solid was collected by filtration, washed with a small amount of H2O and dried to give 5.8 g (84%) of 5 as yellow crystalline solid. Mp 139-140 C. 1H NMR (CDCl3, delta): 4.15 (m, 1H), 5.50 (d, 2H, J = 8.5 Hz), 7.50 (d, 1H, J = 1.9 Hz), 7.95 (d, 1H, J = 1.9 Hz). LCMS m/z: 222 (M-30).To a mixture of 5-iodopyridazin-3 (2H) -one (14.0 g) and DMF (150 mL) were added dropwise diisopropylethylamine (16.3 g) and (2- (trimethylsilyl) ethoxymethyl chloride (21.0 g) under ice-cooling, and the mixture was stirred at 15C for 16 hr.The solvent was evaporated under reduced pressure, and the residue was diluted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethylacetate/petroleum ether) to give the title compound (17.9 g) .XH N R (400 MHz, CDC13) delta 0.00 (9H, s) , 0.96 (2H, t, J = 8.4 Hz), 3.69 (2H, t, J = 8.4 Hz), 5.41 (2H, s) , 7.48 (1H, d, J = 2.0 Hz), 7.93 (1H, d, J = 2.0 Hz).5-Iodopyridazin-3 (2H) -one (200 mg, 0.901 mmol) and methanol (54.7 muL, 1.35 mmol) were charged to a microwave vial equipped with a magnetic stirbar. This was dissolved in THF (4.5 mL) . To this solution was charged di-tert-butyl azodicarboxylate (311 mg, 1.35 mmol) and triphenylphosphine (354 mg, 1.35 mmol) . The reaction mixture was then equipped with a rubber septum and then stirred at room temperature overnight. The reaction mixture was quenched with MeOH and then then concentrated under reduced pressure to give the crude product, which was purified by silica gel column chromatography (0-10 MeOH/DCM) to afford 5-iodo-3-methoxypyridazine. LC/MS: (M+1) +: 236.83To a solution of To a solution of [00214] Step 4: To a solution of To a solution of To a solution of

Molecular Weight:221.98
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:221.92901
Monoisotopic Mass:221.92901
Topological Polar Surface Area:41.5
Heavy Atom Count:8
Complexity:173
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes