Acetone → HCID 112757186, compound

Temperature

0 °C

3-Amino-5-bromopyridine (Aldrich, 5.0 g, 28.9 mmol), acetone (6.37 ml, 87 mmol), Zinc chloride (0.5 M in THF) (11.56 ml, 5.78 mmol) were combined in acetonitrile (150 ml) and cooled to 0° C. The reaction was stirred for 10 min and trimethylsilylcyanide (10.46 ml, 78 mmol) was added dropwise. The reaction was heated to 85° C. in an oil bath with a reflux condensor. The reaction was monitored by LCMS and at 2 hrs the reaction was 80% complete. The reaction was cooled to room temperature and additional acetone (1.2 mL) and trimethylsilylcyanide (3 mL) added. The reaction was allowed to stir 18 hrs at 85° C. The reaction mixture was concentrated to reduce the volume by 50% and mixture poured into brine (100 mL). The pH was adjusted to 7.5 with aq. NaHCO3 and the product extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and resulting solution filtered thru a pad of silica. The filtrate was concentrated and the residue purified by silica gel chromatography, Biotage SNAP 100 g, eluting with EtOAc/isohexane (0-100%) to give 6.42 g, 93% yield of the desired product as an off-white solid, I-4a.

1. temperatureThe reaction was heated to 85° C. in an oil bath with a reflux condensor
2. waitThe reaction was monitored by LCMS and at 2 hrs
3. temperatureThe reaction was cooled to room temperature
4. stirringto stir 18 hrs at 85° C
5. concentrationThe reaction mixture was concentrated
6. additionpoured into brine (100 mL)
7. extractionthe product extracted with ethyl acetate (2×100 mL)
8. washThe combined organic extracts were washed with brine
9. dry with materialdried over Na2SO4
10. customresulting solution
11. filtrationfiltered
12. concentrationThe filtrate was concentrated
13. customthe residue purified by silica gel chromatography, Biotage SNAP 100 g
14. washeluting with EtOAc/isohexane (0-100%)

ORD record

ord-434ada757adf4bed847fd4ddcdd35521

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096598B2