Water → 1-Methyl-4-nitro-1H-indazole

To a solution of 4-nitro indazole [WO-A-0135947] (5.0 g, 31 mmol) in dimethylformamide at 0° C. was added sodium hydride (1.34 g of a 60% dispersion in oil, 34 mmol). The mixture was stirred at room temperature for 10 minutes. Iodomethane (2.28 ml, 37 mmol) was added and the reaction stirred at room temperature for 90 minutes. Water (500 ml) was added and the reaction extracted into ethyl acetate (3×200 ml). The combined organic layers were washed with water (2×200 ml) then dried (Mg2SO4) and evaporated. Trituration overnight in dichloromethane/hexane gives 0.97 g of pure 1-methyl-4-nitro-1H-indazole. The remaining solution was condensed and purified by column chromatography on silica eluting with 40-20% hexane in dichloromethane to give additional 1-methyl-4-nitro-1H-indazole (1.30 g, total 2.27 g, 42%) as the less polar product 1H NMR (360 MHz, CDCl3) 4.18 (3H, s), 7.52 (1H, t, J 8.0), 7.77 (1H, d, J 8.4), 8.15 (1H, d, J 7.7), 8.61 (1H, s); and as the more polar, 2-methyl-4-nitro-2H-indazole (1.50 g, 28%). 1H NMR (400 MHz, CDCl3) 4.32 (3H, s), 7.40 (1H, t, J 8.0), 8.07 (1H, d, J 8.6), 8.18 (1H, d, J 7.6), 8.55 (1H, s).

1. stirringthe reaction stirred at room temperature for 90 minutes
2. extractionthe reaction extracted into ethyl acetate (3×200 ml)
3. washThe combined organic layers were washed with water (2×200 ml)
4. dry with materialthen dried (Mg2SO4)
5. customevaporated

ORD record

ord-70abe21653da4dea86376ea1aa096e8f

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07442701B2