Water → N-(5-Chloropyridin-2-yl)-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]-5-phenylbenzamide Hydrochloride

온도

90 °C

To a stirring solution of N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide (0.29 g, 0.54 mmol), tetrakis (triphenylphosphine)-palladium(0) (35 mg, 0.03 mmol), and phenylboronic acid (81 mg, 0.66 mmol) in toluene (5 mL) was added water (0.55 mL) and a 2 M aqueous sodium carbonate solution (0.55 mL, 1.1 mmol). The mixture was heated to 85-95° C. for 1 h, cooled to room temperature, partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was treated with 0.002 N aqueous hydrochloric acid. To the aqueous phase was added dichloromethane followed by saturated aqueous sodium bicarbonate until pH 8-9. The phases were separated and the organic phase was concentrated. The crude product was purified by RPHPLC, eluting with a gradient from 25% through 65% acetonitrile in 0.05% aqueous hydrochloric acid, to give 0.16 g (57%) of a yellow solid.

1. temperaturecooled to room temperature
2. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
3. additionThe organic phase was treated with 0.002 N aqueous hydrochloric acid
4. additionTo the aqueous phase was added dichloromethane
5. customThe phases were separated
6. concentrationthe organic phase was concentrated
7. customThe crude product was purified by RPHPLC
8. washeluting with a gradient from 25% through 65% acetonitrile in 0.05% aqueous hydrochloric acid

ORD 기록

ord-33190203355d48d0bfc760036286c837

출처 데이터셋

uspto-grants-2004_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06759414B2