Triethylamine → 4-(5-Bromo-2-chloropyridin-3-yl)pyrimidine

Temperature

50 °C

5-Bromo-2-chloronicotinic acid (10.0 g, 42.3 mmol) was treated with thionyl chloride (10.0 mL, 137 mmol) and heated to 50° C. for 18 hours. The volatiles were removed and the resulting crude acyl chloride was treated with 80 mL anhydrous THF, trimethylsilylacetylene (5.98 mL, 42.3 mmol), and copper iodide (322 mg, 1.79 mmol). The suspension was sparged with argon for 30 seconds then dichloropalladium bistriphenylphospine (594 mg, 0.846 mmol) was added followed by triethylamine (6.18 mL, 44.4 mmol). After a brief exotherm, the reaction mixture was stirred at ambient temperature for 1 hour before addition of formamidine hydrochloride (4.09 g, 50.8 mmol), sodium carbonate monohydrate (15.7 g, 127 mmol), and methanol (100 mL). After stirring at ambient temperature (mild exotherm) for 15 minutes, the reaction was heated to reflux for 3 hours. The mixture was then allowed to cool before it was filtered through Celite and concentrated in vacuo. The resulting oil was purified by column chromatography using 10-70% EtOAc/hexanes and triturated with diethyl ether to afford the title compound as a tan, crystalline solid. MS m/z=270 (M+H)+. Calc'd for C9H5BrClN3: 270.52.

1. customThe volatiles were removed
2. customThe suspension was sparged with argon for 30 seconds
3. temperaturethe reaction was heated
4. temperatureto reflux for 3 hours
5. temperatureto cool before it
6. filtrationwas filtered through Celite
7. concentrationconcentrated in vacuo
8. customThe resulting oil was purified by column chromatography
9. customtriturated with diethyl ether

ORD record

ord-05b9262f480f48088bfaf1be1fc23419

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07880000B2