529508-58-5

456-41-7

5401-94-5

529508-58-5

General procedure for the synthesis of 1-[(3-fluorophenyl)methyl]-5-nitro-1H-indazole from 3-fluorobenzyl bromide and 5-nitroindazole: 5-nitroindazole (1 eq.), cesium carbonate (1.1 eq.), and DMF (5 v/v) were added to a reaction vessel. The mixture was heated to 70-80 °C and 3-fluorobenzyl bromide was added slowly and dropwise over 75 min. The progress of the reaction was monitored by HPLC until the area percentage (AP) of the nitroindazole with the combined isomers was less than 2%. After completion of the reaction, the mixture was cooled to 20 °C. The insoluble salt was removed by filtration and the filter cake was washed with DMF (2.7 v/v). Water (1.35 to 1.45 v/v) was added to the filtrate at 15-21 °C to induce crystallization of the product. The crystal slurry was kept for 4 hours and the crystals were subsequently collected by filtration. The crystals were washed sequentially with 2:1 DMF:water mixture (2.1 vol), water (2 vol) and 3:1 cold acetonitrile:water mixture (1.5 vol). The wet filter cake was dried at less than 45 °C until the weight loss (LOD) was less than 1%, giving a final yield of about 49%. The product was confirmed by 1H NMR (CDCl3): δ 5.64 (s, 2H), 6.87 (d, 1H, J = 9.4 Hz), 6.95 (m, 2H), 7.30 (m, 1H), 7.42 (d, 1H, J = 9.2 Hz), 8.23 (dd, 1H, J = 10Hz and 2Hz), 8.26 (s, 1H), 8.72 (d , 1H, J = 2Hz). Mass spectrum (MS): 272 (M + H)+; HPLC retention time: 6.99 min (YMC ODS-A 3 µm, 4.6 x 50 mm column, 10 min gradient, 2.5 mL/min).