2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine → N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4-tert-butylbenzamide

Temperature

95 °C

A 48-mL seal tube equipped with a magnetic stirring bar was charged with 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (5) (1.0 g, 4.0 mmol), N-(3-bromo-2-methylphenyl)-4-tert-butylbenzamide (1.8 g, 5.0 mmol), and tetrakis(triphenylphosphine)palladium (0.20 g, 0.20 mmol) in DME (10 mL) and 1 N sodium carbonate (10 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane (20 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 0-10%, MeOH in dichloromethane, to afford 1.0 g (64%) of N-(3-(5-amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4-tert-butylbenzamide (6) as a solid.

1. customA 48-mL seal tube
2. customequipped with a magnetic stirring bar
3. customAfter the mixture was degassed for 15 min.
4. temperatureThen, the reaction mixture was cooled to room temperature
5. additionpoured into H2O (10 mL)
6. additionTo this was added dichloromethane (20 mL)
7. customthe layers were separated
8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
9. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated
12. customThe crude mixture was purified by column chromatography, gradient 0-10%, MeOH in dichloromethane

ORD record

ord-d8b8b1a520a84de7958ce8eb2839e300

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07838523B2