Sodium Iodide → Methyl 5-amino-6-chloro-2-methylimidazo[1,2-a]pyridine-8-carboxylate

A mixture of methyl 2,6-diamino-5-chloronicotinate (Example 2, Step 3, 15 g, 74.4 mmol), bromoacetone (10.4 mL, 112 mmol) and sodium iodide (16.7 g, 112 mmol) in methanol (700 mL) was stirred under reflux for 22 h. Another 2.5 mL (33 mmol) of bromoacetone was added and the stirring was continued for 24 h. The reaction mixture was quenched with saturated aqueous sodium carbonate and removed methanol in vacuo. The residue was extracted with ethyl acetate (250 mL×10) adding a small amount of methanol to dissolve the organic solid. The organic extracts were dried over sodium sulfate and concentrated. Purification by column chromatography on silica gel eluting with dichloromethane/methanol (20:1) gave a dark brown solid, which was washed with ethyl acetate and filtered to afford 10.5 g (43.9 mmol, 59%) of the title compound as a pale brown solid.

1. temperatureunder reflux for 22 h
2. customThe reaction mixture was quenched with saturated aqueous sodium carbonate
3. customremoved methanol in vacuo
4. extractionThe residue was extracted with ethyl acetate (250 mL×10)
5. additionadding a small amount of methanol
6. dissolutionto dissolve the organic solid
7. dry with materialThe organic extracts were dried over sodium sulfate
8. concentrationconcentrated
9. customPurification by column chromatography on silica gel eluting with dichloromethane/methanol (20:1)
10. customgave a dark brown solid, which
11. washwas washed with ethyl acetate
12. filtrationfiltered

ORD record

ord-de6bb408c67e43998fd4cf42412fdf91

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06951867B2