The general procedure for the synthesis of 7-fluoro-1H-indazole-3-carboxylic acid from 7-fluoroindolomanedione was carried out as follows: with reference to the methodology reported by Johnson, B.L. and Rogers, J.D. in Syn. Commun. 2005, 35, 2681-2684. First, 5.28 g of 7-fluoroindigo was suspended in 30 mL of water under stirring conditions, followed by the addition of a solution of 1.30 g NaOH dissolved in 10 mL of water. Stirring was continued until all solids were completely dissolved to form a deep red solution, which was subsequently cooled in an ice water bath. Next, a pre-cooled (ice bath) solution of 2.21 g NaNO2 dissolved in 10 mL of water was slowly added. The mixed solution was slowly added dropwise to the pre-cooled (ice bath) aqueous sulfuric acid solution (3.4 mL of H2SO4 dissolved in 60 mL of water), with ice being added during the process to maintain the temperature at approximately 0°C. After stirring for about 10 minutes, the dark red diazo solution was slowly added to a pre-cooled (0°C, ice bath) solution of 18 g SnCl2-2H2O dissolved in 30 mL of concentrated HCl, and ice was continued to be added to maintain the temperature at about 0°C. After the reaction mixture was stirred for about 1 h, filtration was performed and the resulting residue was dissolved in 60 mL of 1N NaOH and washed with ether (2 x 50 mL). The yellow-brown solution obtained was cooled in an ice bath and acidified with concentrated HCl to pH 3 (detected using litmus paper), at which point a dark yellow precipitate precipitated. The precipitate was collected by filtration, washed with water and dried in an oven overnight to give 3.69 g (47% yield) of 7-fluoro-1H-indazole-3-carboxylic acid as an orange solid. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 14.35 (br s, 1H), 13.22 (br s, 1H), 7.89-7.87 (m, 1H), 7.26-7.21 (m, 2H). m/z MS (ESI) m/z 181 (M + H)+.
