372118-00-8

Step 2 Synthesis of methyl 4,6-dihydroxypyridazine-3-carboxylate: dimethyl 2-diazo-3-oxoglutarate (50.0 g, 249.8 mmol) and triphenylphosphine (65.5 g, 249.8 mmol) were dissolved in ethyl ether (500 mL) and stirred at room temperature for 24 hours. After the reaction was completed, the organic solvent was removed under vacuum. Acetic acid (500 mL) and water (50 mL) were added to the residue and the reaction was refluxed for 10 hours. The reaction mixture was concentrated under reduced pressure to give a viscous residue. The residue was ground with ethyl acetate to give a yellow solid. The solid was purified by silica gel column chromatography (100-200 mesh, eluent: dichloromethane solution of 1-5% methanol) to give methyl 4,6-dihydroxypyridazine-3-carboxylate (12.8 g, 30% yield) as a yellow solid.LC-MS: m/z 169.2 [M + H]+.

[1] Patent: US2013/178478, 2013, A1. Location in patent: Paragraph 0299;0300
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2683 - 2691
[3] Patent: US2004/77653, 2004, A1. Location in patent: Page 18