反应方程式
COc1nc(N)ccc1-c1cnn(C)c1.Cc1csc(C2CN(C)Cc3c(C)cc(Cl)nc3O2)n1>CC(C)(C)[O-].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].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>COc1nc(Nc2cc(C)c3c(n2)OC(c2nc(C)cs2)CN(C)C3)ccc1-c1cnn(C)c1参与物
反应物 2
产物 1
试剂、催化剂与溶剂 4
反应条件
- 温度
- 100 °C
实验过程
8-chloro-4,6-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (185 mg, 0.60 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (122 mg, 0.60 mmol), Pd2dba3 (13.67 mg, 0.01 mmol), BINAP (18.59 mg, 0.03 mmol) and SODIUM TERT-BUTOXIDE (92 mg, 0.96 mmol) were weighed into a microwave vial. toluene (5 mL) was added and the vial was capped and flushed with argon. The mixture was heated to 100°C in a microwave apparatus for 2 h. The reaction mixture was diluted with dichloromethane and filtered. The solvents were evaporated and the residue was purified by column chromatography on Silica using a gradient of increasing concentration of methanol, from 0 to 8 %, in dichloromethane to give 163 mg og the title product . The enantiomers were separated by HPLC using a chiral stationary phase to give enantiomer 1 of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (66.3 mg, 23.25 %) and enantiomer 2 of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (65.2 mg, 22.86 %).
来源与证据
- ORD记录
- ord-086118e3608c416e9d858ba54c5d1e17
- 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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