Dimethylformamide → 2-Chloro-N-(2-methylpropyl)-6-methyl-3-nitropyridin-4-amine

Temperature

0 °C

2,4Dichloro-6-methyl-3-nitropyridine (39.5 g) from Part A and anhydrous dimethylformamide (400 ml) were combined and cooled to 0° C. Triethylamine (26.6 ml) and then 2-methylpropylamine (20.9 ml) were added to the resulting mixture with mixing. The reaction was complete after 16 hours, as determined by high pressure liquid chromatography (HPLC) and TLC monitoring. The dimethylformamide was removed from the resulting reaction mixture under reduced pressure, and the resulting dark yellow oil was dissolved in ethyl acetate (800 ml). The ethyl acetate solution was washed with water (3×400 ml), dried with magnesium sulfate, and the solvent was removed under reduced pressure. The resulting dark orange oil was dissolved in hexane (400 ml) and cooled to below 0° C. A seed crystal was added, and after 2 hours the resulting crystals were filtered and washed with cold (<0° C.) hexane. The crystals (30.49 g) were found to be pure by NMR analysis.

1. additionwith mixing
2. customThe dimethylformamide was removed from the resulting reaction mixture under reduced pressure
3. dissolutionthe resulting dark yellow oil was dissolved in ethyl acetate (800 ml)
4. washThe ethyl acetate solution was washed with water (3×400 ml)
5. dry with materialdried with magnesium sulfate
6. customthe solvent was removed under reduced pressure
7. dissolutionThe resulting dark orange oil was dissolved in hexane (400 ml)
8. temperaturecooled to below 0° C
9. additionA seed crystal was added
10. filtrationafter 2 hours the resulting crystals were filtered
11. washwashed with cold (<0° C.) hexane

ORD record

ord-4682bcd5d7f14dbb94b23441a35cd3ca

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743920B2