2-Aminopyridine → 2-Chloromethyl-imidazo(1,2-A)pyridine

1,3-Dichloroacetone (22.9 g, 180.3 mmol) was added to a solution of 2-amino pyridine (10 g, 106.3 mmol) in acetonitrile (200 ml). The mixture was heated at reflux for 14 h (the reaction was monitored by TLC). Upon completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water and adjusted the pH to 7.5 with sodium bicarbonate solution which was extracted with EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 12% ethyl acetate in n-hexanes and silica gel (230-400 mesh) to afford 2-(chloromethyl) imidazo[1,2-a]pyridine (8.0 g, 47.9%,) as pale yellow solid. 1H NMR: 200 MHz, CDCl3: δ 8.15 (d, 1H), 7.6 (dd, 2H), 7.1 (t, 1H), 6.8 (t, 1H), 4.75 (s, 2H). MS: [M+H]+: m/z=167.2.

1. temperatureThe mixture was heated
2. temperatureat reflux for 14 h (the reaction
3. customUpon completion of the reaction
4. customthe volatiles were removed under reduced pressure
5. additionThe residue was diluted with water
6. extractionwas extracted with EtOAc
7. dry with materialThe combined organics were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by flash column chromatography

ORD record

ord-98e76c9cf0624f208fa372286faa9576

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946222B2