3,5-Dibromo-1-methylpyridin-2(1H)-one → N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

온도

95 °C

In a 48 mL sealed tube equipped with a magnetic stirring bar was placed 5-bromo-2-methoxypyridin-3-amine (16) (1.0 g, 4.0 mmol), N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (1(2.4 g, 6.7 mmol), and Pd(PPh3)4 (0.30 g, 0.20 mmol) in DME/1N Na2CO3 (10 mL, 1/1). After the reaction mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the mixture was cooled to room temperature and diluted with dichloromethane (10 mL) and H2O (10 mL), and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-25% MeOH in dichloromethane, to afford 1.0 g (65%) of N-(3-(5-amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (17) as a solid.

1. customIn a 48 mL sealed tube
2. customequipped with a magnetic stirring bar
3. customAfter the reaction mixture was degassed for 15 min.
4. temperatureThen, the mixture was cooled to room temperature
5. additiondiluted with dichloromethane (10 mL) and H2O (10 mL)
6. customthe layers were separated
7. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
8. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated
11. customThe crude mixture was purified by column chromatography, gradient 0-25% MeOH in dichloromethane

ORD 기록

ord-437d079a894d4149bc5f5440032eea06

출처 데이터셋

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08058446B2