反应方程式
CN1CCC(CN)CC1.Cl.FC(F)(F)Oc1cccc(-c2cnc3ccc(Cl)nn23)c1>CC(C)(C)[O-].CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1.Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].[Pd]>CN1CCC(CNc2ccc3ncc(-c4cccc(OC(F)(F)F)c4)n3n2)CC1参与物
反应条件
- 温度
- 110 °C
实验过程
A 50 mL round bottom flask was charged with a magnetic stir bar, toluene (6.376 mL), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine hydrochloride (200 mg, 0.57 mmol), (1-methylpiperidin-4-yl)methanamine (110 mg, 0.86 mmol), 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (67.4 mg, 0.17 mmol), Pd2dba3 (52.3 mg, 0.06 mmol), and sodium tert-butoxide (220 mg, 2.28 mmol). The mixture was degassed with argon, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 110 °C with stirring for 16 h. The mixture was cooled to rt, pre-absorbed onto silca gel (~ 20 g) and purified on silica gel (80 g) using MeOH/DCM (1:3) as eluent to afford the title compound ~ 90 % pure. This material was then dissolved in DMSO and purified via reverse phase HPLC water/MECN (5->55%, 12 min) as eluent. The pure fractions were collected and converted to the corresponding HCl salt to afford N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (125 mg, 49.5 %) hydrochloride as a white solid.
来源与证据
- ORD记录
- ord-eeacd9f15ab048189aee22e65e39160d
- 来源数据集
- 750 AstraZeneca ELN dataset
- 原始链接
- 查看来源
关联笔记
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