Toluene → 5-(Pyrazin-2-yl)pyridin-2-amine

Temperature

90 °C

To a sealed tube was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine 86-1 (2.2 g, 10 mmol), 2-iodopyrazine 86-2 (2.06 g, 10 mmol), Pd(PPh3)4 (577 mg, 0.5 mmol), toluene (70 mL), ethanol (15 mL) and 2M Na2CO3 (15 mL). The reaction mixture was bubbled with nitrogen for 2 minutes and stirred at 90° C. for 10 hours. After cooling to room temperature, the solvents were evaporated and the residue was redissolved in dichloromethane (200 ml) and treated with 1M HCl aqueous solution (50 mL). The two layers were separated and the aqueous layer was treated with 10% NaOH aqueous solution to adjust the pH to around 13. The resulting suspension was extracted with ethyl acetate (100 mL×3). The combined organic phases were washed with H2O (50 mL) and brine (50 mL), dried over Na2SO4, and concentrated to give 5-(pyrazin-2-yl)pyridin-2-amine 86-3 as white solid. MS m/z 173.1 (M+1); 1H NMR 400 MHz (DMSO-d6) δ 9.12(d, 1H, J=1.6 Hz), 8.73(m, 1H), 8.60(m, 1H), 8.46(d, 1H, J=2.8 Hz), 8.12(dd, 1H, J1=8.8 Hz, J2=2.4 Hz), 6.55(d, 1H, J=8.8 Hz), 6.46(s, 2H).

1. customThe reaction mixture was bubbled with nitrogen for 2 minutes
2. temperatureAfter cooling to room temperature
3. customthe solvents were evaporated
4. dissolutionthe residue was redissolved in dichloromethane (200 ml)
5. additiontreated with 1M HCl aqueous solution (50 mL)
6. customThe two layers were separated
7. additionthe aqueous layer was treated with 10% NaOH aqueous solution
8. extractionThe resulting suspension was extracted with ethyl acetate (100 mL×3)
9. washThe combined organic phases were washed with H2O (50 mL) and brine (50 mL)
10. dry with materialdried over Na2SO4
11. concentrationconcentrated

ORD record

ord-e0a48ecec504447c947630af26796a41

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238646B2