Phosphorus oxychloride → 4-Chloro-2-(ethoxymethyl)-1-(2-methylpropyl)-6-methyl-1H-imidazo[4,5-c]pyridine

Temperature

135 °C

N-[2-Chloro-4-(2-methylpropylamino)-6-methylpyridin-3-yl]-2-ethoxyacetamide (3.64 g), anhydrous toluene (100 ml), and phosphorus oxychloride (10.2 ml) were combined in a sealed glass tube and heated to 135° C. for 16 hours. The resulting reaction mixture was cooled, and the phosphorus oxychloride and toluene were removed under reduced pressure. The resulting black oil was dissolved in ethyl acetate, and the resulting solution was washed with saturated aqueous sodium bicarbonate. The basic aqueous layer was then washed with ethyl acetate. The organic layers were combined and concentrated to a black oil under reduced pressure. The oil was put through a column of silica gel using 60/40 ethyl acetate/hexane. The resulting eluted solution was dried under reduced pressure to a brown oil, which solidified after sitting for 48 hours. NMR analysis of the resulting product (2.59 g) indicated only minor impurities, and the product was carried on to the next step.

1. customThe resulting reaction mixture
2. temperaturewas cooled
3. customthe phosphorus oxychloride and toluene were removed under reduced pressure
4. dissolutionThe resulting black oil was dissolved in ethyl acetate
5. washthe resulting solution was washed with saturated aqueous sodium bicarbonate
6. washThe basic aqueous layer was then washed with ethyl acetate
7. concentrationconcentrated to a black oil under reduced pressure
8. washThe resulting eluted solution
9. customwas dried under reduced pressure to a brown oil, which

ORD record

ord-8579ec6ebef345489bc0dd23ad52e1d7

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743920B2