Hydrochloric Acid → (4-(6-Aminopyridin-3-yl)-3-fluorophenyl)boronic acid

Temperature

80 °C

5-(4-Chloro-2-fluorophenyl)pyridin-2-amine (2.0 g, 9.0 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.9 g, 11.0 mmol), chloro(2-dicyclohexyl-phosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.14 g, 0.18 mmol), and KOAc (2.7 g, 27 mmol) were combined in a sealable reaction vessel under nitrogen, and then treated with anhydrous 1,4-dioxane (100 mL, sparged with nitrogen). The vessel was sealed and then heated at 80° Celsius for 16 hours. The mixture was cooled to rt, HCl (1 m, 50 mL) was added and the mixture stirred for 20 min. The mixture was then diluted with EtOAc (200 mL) and the aqueous phase was collected. The organic phase was extracted with 1 M HCl (2×75 mL). The combined aqueous phases were cooled in an icebath and the pH was adjusted to ca. 7 using solid sodium bicarbonate. The resulting precipitate was collected by filtration, washed well with water, and dried to provide the title compound (2.1 g, 98%). MS (CI): mass calcd. for C11H10BFN2O2, 232.08; m/z found, 233.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.29-8.20 (s, 2H), 8.18-8.13 (s, 1H), 7.80-7.72 (m, 1H), 7.69-7.63 (m, 1H), 7.63-7.57 (m, 1H), 7.51-7.44 (m, 1H), 6.84-6.57 (m, 3H).

1. customThe vessel was sealed
2. temperatureThe mixture was cooled to rt
3. customthe aqueous phase was collected
4. extractionThe organic phase was extracted with 1 M HCl (2×75 mL)
5. temperatureThe combined aqueous phases were cooled in an icebath
6. filtrationThe resulting precipitate was collected by filtration
7. washwashed well with water
8. customdried

ORD record

ord-3e45b1415977403f98d0d1bc9c884f7e

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09079866B2