3-Aminopyridine → N-pyridin-3-ylpyridin-3-amine

温度

100 °C

Stock solution: 2.43 M solution of CyPF-tBu/Pd(OAc)2 (1:1) in DME. 3-bromopyridine (6 mL, 62.28 mmol) was dissolved in DME (10 mL). To the solution was added 10 mL of stock solution, and sodium tert-butoxide (8.38 g, 87.19 mmol). To the mixture was added a solution of pyridin-3-amine (7.03 g, 74.74 mmol) in DME (10 mL). The mixture was heated at 100 °C overnight. LCMS showed the product formation, and the starting material 3-BrPy . To the mixture was added 4 mL stock solution additionally, and the mixture was heated at 100 °C for another 5h. LCMS showed more impurities peaks. The mixture was filtered. The filtrate was concentrated, and the compound was purified by preparative HPLC on a XBridge C18 column (10 µm 250x50 ID mm) using a gradient of 0-50% acetonitrile in H2O/ACN/NH3 95/5/0.2 buffer over 15 minutes with a flow of 100 mL/min. The compounds were detected by UV at 254nm. To the fractions (ca. 1000mL) were added 20 mL of HOAc. The product was freezing- dried to give the 1.56 g of product. But NMR1 showed that there was 5 eq. acetic acid in the crude. The residue was dissolved in 10 mL methanol. To the solution was added 10 mL of aq. ammonia solution, and the crude was freezing- dried overnight to give the product dipyridin-3-ylamine (1.300 g, 12.19 %) .

ORDレコード

ord-d32527b9fef34013a5ae697e40e160a3

出典データセット

750 AstraZeneca ELN dataset

元リンク

出典を表示