1,3-Dichloroacetone → 2-(chloromethyl)-5-methylimidazo[1,2-a]pyridine

1,3-Dichloroacetone (17.6 g, 138.3 mmol) was added to a solution of 6-methylpyridin-2-amine (10 g, 92.5 mmol) in acetonitrile (200 ml). The mixture was heated at reflux for 14 h (the reaction was monitored by TLC). The mixture was concentrated under reduced pressure, the residue was diluted with water, and the pH was adjusted to 7.5 with sodium bicarbonate solution. The mixture 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 10% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 2-(chloromethyl)-5-methylimidazo[1,2-a]pyridine (7.0 g, 70.7%,) as a pale yellow solid. 1H NMR: 200 MHz, CDCl3: δ 8.15 (s, 1H), 7.6 (dd, 2H), 7.1 (t, 1H), 6.8 (t, 1H), 4.95 (s, 2H), 2.6 (s, 3H). MS: [M+H]+: m/z=181.5.

1. temperatureThe mixture was heated
2. temperatureat reflux for 14 h (the reaction
3. concentrationThe mixture was concentrated under reduced pressure
4. additionthe residue was diluted with water
5. extractionThe mixture was extracted with EtOAc
6. dry with materialthe combined organics were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by flash column chromatography

ORD record

ord-ce3fa98e82264417813df0c2e33c88dd

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946222B2