Electric Literature of 1018505-59-3, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 1018505-59-3 as follows.
To a solution of 3-chloro-7-(2, 6-dichloro-3, 5-dimethoxyphenyl) isoqinoline (600 mg, 1.628 mmol), 5-(4-ethylpiprazine-l-yl) pyridine-2-amine (step 3.1) (376 mg, 1.82 mmol), X-Phos (77.60 mg, 10 mol %) and cesium carbonate (1.06 g, 1.25 mmol) in Toluene (15 mL) and t- BuOH (5 mL) (4: 1) argon was purged for 20 min. Then was added Pd2 (dba)3 (149 mg, 10 mol %) again argon was purged for 5 min. The reaction mixture was heated at 120C overnight. The reaction mixture was cooled to room temperature and filtered through celite pad and filtrate was concentrated under reduced pressure. Product was purified by column chromatography on silica gel column using DCM: MeOH: NH3 aq. (95:5: 1%) as an eluent to afford 7-(2, 6-dichloro-3, 5-dimethoxyphenyl)-N-[5-(4-ethylpiperazin-l-yl) pyridin-2-yl] isoquinoline-3 -amine (600 mg) as a pale yellow solid. 1H NMR (400 MHz, CDC13) delta 8.97 (s, 1H), 8.09 (dd, J = 25.7, 7.3 Hz, 2H), 7.82 – 7.68 (m, 2H), 7.41 (dd, J = 8.5, 1.6 Hz, 1H), 7.32 (dd, J = 8.9, 2.9 Hz, 1H), 7.17 – 7.10 (m, 1H), 6.65 (s, 1H), 3.99(s, 6H), 3.26 – 3.16 (m, 4H), 2.71 – 2.62 (m, 4H), 2.51 (q, J = 7.2 Hz, 2H), 1.15 (t, J= 7.2 Hz, 3H). M/Z: 537.1, M+l : 538.6, tR= 0.81 min. (System 1)
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1018505-59-3, its application will become more common.
Reference:
Patent; EVOTEC (UK) LTD.; MC CARTHY, Clive; MILLS, Matthew; WO2014/44846; (2014); A1;,
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