General procedure for the synthesis of 6-bromoindazole-3-carboxylic acids from 6-bromodihydroindole-2,3-dione: The conversion of substituted indirubic acids to the corresponding indazole-3-carboxylic acids was carried out in essentially the same way as described by Snyder, H.R. et al. This was done as follows: first, the substituted indigo (22.1 mmol) was diluted with 1N sodium hydroxide solution (24 mL) and heated at 50 °C for 30 min. Subsequently, the resulting burgundy-colored solution was cooled to room temperature and kept for 1 hour. Next, the reaction mixture was cooled to 0 °C and treated with an aqueous solution (5.5 mL) of sodium nitrite (22.0 mmol) at 0 °C. The solution was slowly added via a pipette submerged below the surface of a vigorously stirred aqueous solution of sulfuric acid (2.3 mL) (45 mL) at 0°C. The addition process lasted for 15 min, after which the reaction mixture was held for an additional 30 min. Then, a cold (0°C) solution of concentrated hydrochloric acid (20 mL) of tin(II) chloride dihydrate (52.7 mmol) was added to the reaction mixture over a period of 10 minutes and the reaction mixture was held for 60 minutes. Upon completion of the reaction, the precipitated solid was separated by filtration, washed with water and dried to give a quantitative product. The product was of sufficient purity (confirmed by 1H NMR and LC/MS) to be used in the next step without further purification. Alternatively, the acid can be purified by recrystallization from acetic acid to obtain a higher purity substance. The following acids can also be prepared using this method: 6-bromo-1H-indazole-3-carboxylic acid, 5-methoxy-1H-indazole-3-carboxylic acid and 6-methoxy-1H-indazole-3-carboxylic acid.
