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

Temperature

0 °C

2,4-Dichloro-6-methyl-3-nitropyridine (28.75 g) and anhydrous dimethylformamide (300 ml) were combined and cooled to 0° C. Triethylamine (19.4 ml) and then 2-methylpropylamine (13.8 ml) were added to the resulting mixture. The reaction was not complete as determined by HPLC and TLC after 16 hours. An additional 1.38 ml of 2-methylpropylamino was added to the reaction mixture, and after another hour the reaction was complete. The dimethylformamide was removed from the resulting reaction mixture under reduced pressure, and the resulting dark yellow oil was dissolved in ethyl acetate. The ethyl acetate solution was washed with water (3×), dried with magnesium sulfate, and the solvent was removed under reduced pressure. The resulting yellow oil was dissolved in hexane and cooled to below 0° C. overnight. A yellow solid formed. The yellow solid was washed with cold (<0° C.) hexane and filtered. The remaining crystals (22.02 g) were found to be pure by NMR analysis and used in the next step.

1. additionAn additional 1.38 ml of 2-methylpropylamino was added to the reaction mixture
2. waitafter another hour the reaction was complete
3. customThe dimethylformamide was removed from the resulting reaction mixture under reduced pressure
4. dissolutionthe resulting dark yellow oil was dissolved in ethyl acetate
5. washThe ethyl acetate solution was washed with water (3×)
6. dry with materialdried with magnesium sulfate
7. customthe solvent was removed under reduced pressure
8. dissolutionThe resulting yellow oil was dissolved in hexane
9. temperaturecooled to below 0° C. overnight
10. customA yellow solid formed
11. washThe yellow solid was washed with cold (<0° C.) hexane
12. filtrationfiltered

ORD record

ord-6890432416ee43aab46c75d95aea8d12

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743920B2