With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.933-76-6,4,5-Dichloro-2-methylpyridazin-3(2H)-one,as a common compound, the synthetic route is as follows.
933-76-6, Step 1: 4-bromo-5-chloro-2-methy]pyridazin-3(2H)-one 4,5-dichloro-2-methylpyridazin-3(2H)-one (180 mg, 1.01 mmol) was dissolved in 48% aqueous HBr (5 mL, 45 mmol). The reaction mixture was heated at 100 C for 16 hours. The reaction mixture was cooled down and basified up to pH = 8 with 1M aq. NaOH. The mixture was extracted with EtOAc. The organic layer was washed with brine, dried with Na2S04, filtered and evaporated under reduced pressure to afford a mixture of 4-bromo-5-chloro-2-methylpyridazin- 3(2H)-one and 5-bromo-4-chloro-2-methylpyridazin-3(2H)-one (280 mg, 1.253 mmol) in quantitative yield. LCMS (ESI+): 223 / 225 / 227 (M+H , Br, CI pattern). Step 2: 4-brorao-2-methyl-5-((l-methylazepan-3-yI)amiao)pyridaziii-3(2H)- The 4-bromo-5-chloro-2-methylpyridazin-3(2H)-one and 5-bromo-4-chloro-2-methylpyridazin- 3(2H)-one (280 mg, 1.253 mmol), l-methylazepan-3 -amine (0.209 g, 1.63 mmol), N-ethyl-N- isopropylpropan-2-amine (0.243 g, 1.88 mmol) and n-BuOH (1.5 mL) were charged in a microwave vial. The reaction was heated to 160 C for 60 min. The mixture of regioisomers was purified by flash chromatography (10% to 100% of 1 : 10:90 NH4OH:MeOH:DCM in DCM eluent gradient) to afford two sets of fractions. The later eluting fractions (most polar compound) were combined and evaporated under reduced pressure to afford 4-bromo-2-methyl- 5-((l -methylazepan-3-yl)amino)pyridazin-3(2H)-one (155 mg, 0.395 mmol) in 39% yield. lH NMR (400MHz, DMSO-d6) delta 7.77 (s, 1H), 6.20 (d, J= 8.8 Hz, 1H), 3.96 (br. s, 1 H), 3.57 (s, 3H), 2.55-2.75 (m, 3H), 2.34-2.45 (m, 1H), 2.37 (s, 3H), 1.31-1.74 (m, 6H). LCMS (ESI+): 315 / 317 (M+H, Br pattern).
The synthetic route of 933-76-6 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; ALBRECHT, Brian, K.; BURDICK, Daniel, J.; COTE, Alexandre; DUPLESSIS, Martin; NASVESCHUK, Christopher, G.; TAYLOR, Alexander, M.; (117 pag.)WO2016/112298; (2016); A1;,
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