6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-ylamine → N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(tetrahydrofuran-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

温度

100 °C

6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (205 mg, 1.00 mmol), Pd2(dba)3 (22.99 mg, 0.03 mmol), BINAP (31.3 mg, 0.05 mmol) and SODIUM TERT- BUTOXIDE (193 mg, 2.01 mmol) were placed in a round bottomed flask. The flask was stoppered with a septum and flushed with argon. To this was added a solution of 8-chloro-4,6-dimethyl-2-(tetrahydrofuran-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (284 mg, 1.00 mmol) in toluene (5 mL) and the resulting mixture was heated to 100°C for 5 h. The reaction mixture was diluted with dichloromethane and filtered, and the solvent was evaporated. The residue was purified by column chromatography on Silica using gradient elution with increasing concentration of methanol, from 0 to 8 %, in dichloromethane to give a mixture of the two diastereoisomers. The major isomer was precipitated from methanol once and from ethanol twice to give 45 mg of Isomer 1 of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(tetrahydrofuran-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (45 mg, 10 %) as a single diastereoisomer of unknown stereochemistry. The rest of the material was purified by HPLC to give Isomer 1 (115.7 mg, 25.6 %) and Isomer 2 (39 mg, 8.6 %) of N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(tetrahydrofuran-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine.

ORDレコード

ord-b9b3987212a34b6286e3f0f13f180d9b

出典データセット

750 AstraZeneca ELN dataset

元リンク

出典を表示