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

To a solution of 1,3-dichloropropan-2-one (1.40 g, 11 mmol) in 1,2-dimethoxyethane (5 mL), pyridin-2-amine (0.94 g 10 mmol) was added. The solid dissolved immediately and a white precipitate was observed. The mixture was stirred at room temperature for 1 h, and then was cooled to 0° C. for 20 min. The resulting mixture was filtered to give a white solid. The precipitate was suspended in ethanol (EtOH) (40 mL) and heated at reflux to render a clear solution. After refluxing for 2 h, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in water and saturated aqueous NaHCO3 solution was added to adjust the pH to ˜7.0. A white suspension formed during the course of addition. The resulting mixture was stirred for 20 min and then filtered to give the title compound as a white solid (0.5 g, 30% yield). ESI MS: m/z 167 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.49 (d, J=6.8 Hz, 1H), 7.97 (s, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.23 (t, J=7.6 Hz, 1H), 6.88 (t, J=6.4 Hz, 1H), 4.82 (s, 2H).

1. dissolutionThe solid dissolved immediately
2. temperaturewas cooled to 0° C. for 20 min
3. filtrationThe resulting mixture was filtered
4. customto give a white solid
5. temperatureheated
6. temperatureat reflux
7. temperatureAfter refluxing for 2 h
8. concentrationthe reaction mixture was concentrated under reduced pressure
9. dissolutionThe residue was dissolved in water
10. additionsaturated aqueous NaHCO3 solution was added
11. customA white suspension formed during the course of addition
12. stirringThe resulting mixture was stirred for 20 min
13. filtrationfiltered

ORD record

ord-6f2a2a74c4a64f25b2c9ed69dcfc960c

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249162B2