Methanol → HCID 67334590, compound

To a solution of 2-bromo-3-hydroxy-6-iodopyridine (8-2, 10 g, 33.3 mmol, 1.0 equiv) in DMF (104 ml) was added TBAI (1.23 g, 3.33 mmol, 0.1 equiv), diisopropylethylamine (17.5 mL, 100 mmol, 3.0 equiv) and SEM-Cl (8.87 mL, 50.0 mmol, 1.5 equiv). The system was stirred at ambient temperature for 24 hours. The reaction was partitioned between EtOAc and saturated NaHCO3. The organic phase was washed with NaHCO3 and dried over MgSO4. After concentration, the residue was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes) to afford a pale yellow oil. To this pale yellow oil in DMF (145 mL) was added a 4.37M solution of NaOMe in MeOH(6.65 mL, 29.1 mmol, 1.0 equiv) and the system was heated to 100° C. for 1 hour. The system was cooled to ambient temperature and partitioned between EtOAc and saturated NaHCO3. The organic phase was washed with brine and dried over MgSO4. After concentration, the residue was purified by normal phase column chromatography (0 to 20% EtOAc in hexanes) to afford a clear oil. To this clear oil in DMF (69 mL) was added CuCN (3.71 g, 41.4 mmol, 2.0 equiv) and the system was irradiated at 160° C. for 0.5 hour. The reaction mixture was filtered through celite and partitioned between EtOAc and brine. The organic phase was dried over MgSO4 and concentrated. The residue was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes) to afford a yellow solid. ESI+MS[M+H]+C7H6N2O2=151.0

1. customThe reaction was partitioned between EtOAc and saturated NaHCO3
2. washThe organic phase was washed with NaHCO3
3. dry with materialdried over MgSO4
4. concentrationAfter concentration
5. customthe residue was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes)
6. customto afford a pale yellow oil
7. temperaturethe system was heated to 100° C. for 1 hour
8. temperatureThe system was cooled to ambient temperature
9. custompartitioned between EtOAc and saturated NaHCO3
10. washThe organic phase was washed with brine
11. dry with materialdried over MgSO4
12. concentrationAfter concentration
13. customthe residue was purified by normal phase column chromatography (0 to 20% EtOAc in hexanes)
14. customto afford a clear oil
15. customthe system was irradiated at 160° C. for 0.5 hour
16. filtrationThe reaction mixture was filtered through celite
17. custompartitioned between EtOAc and brine
18. dry with materialThe organic phase was dried over MgSO4
19. concentrationconcentrated
20. customThe residue was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes)
21. customto afford a yellow solid

ORD record

ord-cb69f71f22c149408cae3f3f79658be8

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592457B2