2-Amino-N-methoxybenzamide → N-methoxy-2-[[5-(trifluoromethyl)-2-[(1,3,5-trimethylpyrazol-4-yl)amino]pyridin-4-yl]amino]benzamide

温度

90 °C

2-amino-N-methoxybenzamide (541 mg, 3.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (166 mg, 0.29 mmol), cesium carbonate (1249 mg, 3.83 mmol) and diacetoxypalladium (38.7 mg, 0.17 mmol) were added to a stirred solution of 4-iodo-5-(trifluoromethyl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyridin-2-amine (759 mg, 1.92 mmol) dissolved in dioxane (20 mL) in a µwave vial at RT. Argon was let to bubble in the mixture for 5 minutes and the resulting slurry was then stirred at 90 °C for 15 hours. Lcms showed complete reaction. The reaction mixture was allowed to cool to room temperature, diluted with dichloromethane, filtered, silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel eluting with 30 to 100% ethyl acetate in petroleum ether. The solvent was evaporated to dryness, the remainning gum was taken up in DCM and concentrated in the cold. The precipitate was collected by filtration, washed with diethyl ether and dried to a constant weight to afford N-methoxy-2-(5-(trifluoromethyl)-2-(1,3,5-trimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)benzamide (742 mg, 89 %) (batch EN03692-99-01) as a off-white solid. NMR showed the presence of solvents (ethyl acetate and diethyl ether). The solid was then dried several days under vacuum at 55°C to removed these solvents (--> batch EN03692-99-02 (723 mg, 1.664 mmol, 87 %)) : unsuccessfully! **Analysis: - NMR (CDE) -- > strenght = 95%, ****ethyl acetate** **= 0.06 mole/mole and diethyl ether = 0.11 mole/mole** ** \- analytical lcms (DDO) --> purity = 99%**

ORDレコード

ord-3db391e974974fdaa88ec87b15c89118

出典データセット

750 AstraZeneca ELN dataset

元リンク

出典を表示