2-Chloronicotinonitrile → 2-(Thiophen-3-yl)pyridine-3-carbonitrile

Temperature

90 °C

To an oven-dried, N2-purged, 50 mL, round-bottomed flask containing a magnetic stir bar were added potassium fluoride (767 mg, 13.2 mmol), bis(tri-t-butylphosphine)palladium (51.0 mg, 0.10 mmol), tris(dibenzylideneacetone)dipalladium 46 mg, 0.05 mmol), 2-chloro-3-cyanopyridine (559 mg, 4.00 mmol), and 3-thiopheneboronic acid (819 mg, 6.4 mmol). The flask was sealed with a septum and purged with dry N2 atmosphere. Anhydrous dioxane (4 mL) was added via syringe. The reaction mixture was heated to ˜90° C. in an oil bath for 18 hours. After cooling to room temperature, ethyl acetate (15 mL) was added and the mixture was filtered through a pad of silica. The filtrate was concentrated by rotary evaporator to give a brown oil. The product was purified by recrystallization from ethyl acetate/hexanes to give 417 mg (56%) of the title compound as a beige solid. MS (ESI−) m/z 186.9 (M+H)+; 1H NMR (CDCl3) δ 7.30 (7.8, 4.7 Hz, 1H), 7.44 (dd, J=5.3, 2.9 Hz, 1H), 7.88 (dd, J=5.1, 1.4 Hz, 1H), 8.03 (dd, J=8.0, 1.9 Hz, 1H), 8.29 (dd, J=3.0, 1.4 Hz, 1H), 8.82 (dd, J=4.7, 1.7 Hz, 1H).

1. customTo an oven-dried, N2-purged
2. addition50 mL, round-bottomed flask containing a magnetic stir bar
3. customThe flask was sealed with a septum
4. custompurged with dry N2 atmosphere
5. additionAnhydrous dioxane (4 mL) was added via syringe
6. temperatureAfter cooling to room temperature
7. additionethyl acetate (15 mL) was added
8. filtrationthe mixture was filtered through a pad of silica
9. concentrationThe filtrate was concentrated by rotary evaporator
10. customto give a brown oil
11. customThe product was purified by recrystallization from ethyl acetate/hexanes

ORD record

ord-ed56c9cd6b1440dc9692aee5050d851b

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07704997B1