Dimethylformamide → HCID 71075900, compound

Temperature

45 °C

To a 100 mL round bottom flask adapted for magnetic stirring and equipped with a nitrogen inlet was charged (3-chlorophenyl)boronic acid (5 g, 32 mmol), 3,5-dichloro-2-cyanopyridine (5.8 g, 34 mmol), K2CO3 (5.5 g, 40 mmol), [1,1′-bis(diphenyphosphino)ferrocene]dichloro-palladium(II) [PdCl2(dppf)] (0.1 g, 0.13 mmol), dimethylformamide (50 mL) and water (5 mL). The reaction solution was agitated and heated to 45° C. and held at that temperature for 18 hours after which the reaction was determined to be complete due to the disappearance of 3,5-dichloro-2-cyanopyridine as measured by TLC analysis using ethyl acetate/methanol (4:1) as the mobile phase and UV 435 nm to visualize the reaction components. The reaction solution was then cooled to room temperature and the contents partitioned between ethyl acetate (250 mL) and saturated aqueous NaCl (100 mL). The organic phase was isolated and washed a second time with saturated aqueous NaCl (100 mL). The organic phase was dried for 4 hours over MgSO4, the MgSO4 removed by filtration and the solvent removed under reduced pressure. The residue that remained was then slurried in methanol (50 mL) at room temperature for 20 hours. The resulting solid was collected by filtration and washed with cold methanol (50 mL) then hexanes (60 mL) and dried to afford 5.8 g (73% yield) of an admixture containing a 96:4 ratio of the desired regioisomer. 1H NMR (DMSO-d6) δ 9.12 (d, 1H), 8.70 (d, 1H), 8.03 (t, 1H) 7.88 (m, 1H), and 7.58 (m, 2H).

1. customTo a 100 mL round bottom flask adapted
2. customequipped with a nitrogen inlet
3. stirringThe reaction solution was agitated
4. customthe reaction components
5. temperatureThe reaction solution was then cooled to room temperature
6. customthe contents partitioned between ethyl acetate (250 mL) and saturated aqueous NaCl (100 mL)
7. customThe organic phase was isolated
8. washwashed a second time with saturated aqueous NaCl (100 mL)
9. dry with materialThe organic phase was dried for 4 hours over MgSO4
10. customthe MgSO4 removed by filtration
11. customthe solvent removed under reduced pressure
12. waitThe residue that remained was then slurried in methanol (50 mL) at room temperature for 20 hours
13. filtrationThe resulting solid was collected by filtration
14. washwashed with cold methanol (50 mL)
15. dry with materialhexanes (60 mL) and dried
16. customto afford 5.8 g (73% yield) of an admixture
17. additioncontaining a 96:4 ratio of the desired regioisomer

ORD record

ord-100a941a5b614a1ea2ca794a0ac44023

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145366B2