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

A mixture of 2-aminopyridine (Aldrich; 0.487 g), 1,3-dichloroacetone (Aldrich; 0.73 g), and dimethoxyethane (6 mL) is stirred at room temperature for 2.5 h and then at 60° C. for 30 min. Dimethoxyethane is then removed under reduced pressure and ethanol (10 mL) is added. The mixture is stirred at 80° C. for 20 min and then cooled and concentrated under reduced pressure. The residue is partitioned between dichloromethane and aq. sodium bicarbonate and the organic layers are filtered through sodium sulfate and concentrated. Dichloromethane and ethyl acetate are added to the residue and the solids are removed by filtration. The filtrate is concentrated and the residue is chromatographed on silica gel using ethyl acetate/hexane (50/50) to give 0.495 g of 2-(chloromethyl)imidazo[1,2-a]pyridine; mp >255° C.; 1H NMR (CDCl3) δ4.78, 6.80, 7.19 7.58, 7.62, 8.08.

1. waitat 60° C. for 30 min
2. customDimethoxyethane is then removed under reduced pressure and ethanol (10 mL)
3. additionis added
4. stirringThe mixture is stirred at 80° C. for 20 min
5. temperaturecooled
6. concentrationconcentrated under reduced pressure
7. customThe residue is partitioned between dichloromethane and aq. sodium bicarbonate
8. filtrationthe organic layers are filtered through sodium sulfate
9. concentrationconcentrated
10. additionDichloromethane and ethyl acetate are added to the residue
11. customthe solids are removed by filtration
12. concentrationThe filtrate is concentrated
13. customthe residue is chromatographed on silica gel

ORD record

ord-066de0fbb5954eb9af7e7fdd42040759

Source dataset

uspto-grants-1999_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05912246