Synthesis
General procedure for the synthesis of 5-iodo-1H-indazole from 5-aminoindazole:
1. a solution of sodium nitrite (2.7 g, 39.1 mmol) in water (40 ml) was slowly added dropwise to a solution of 1-H-indazol-5-amine (5.2 g, 39.1 mmol) in 6 at 0 °C.
2. N hydrochloric acid (73.7 ml) was added to the above mixture at 0°C.
3. the resulting mixture was added slowly and dropwise to a solution of potassium iodide (26.9 g, 162 mmol) in water (60 ml) at 0 °C.
4. The reaction mixture was stirred at room temperature for 3 hours.
5. After completion of the reaction, the reaction mixture was extracted with ethyl acetate (4 x 30 ml).
6. The organic phases were combined and washed sequentially with 10% w/v sodium thiosulfate solution (4 x 30 ml) and brine (2 x 30 ml).
7. The organic phase was dried with anhydrous magnesium sulfate and then concentrated to give a brown solid product.
8. Yield: 8.64 g (90% of theoretical). 9.
9. The structure of the product was confirmed by 3C-NMR (101 MHz, CDCl3, δppm): 84.4, 111.7, 125.6, 129.9, 133.4, 135.4, 139.0.
References
[1] Patent: WO2008/71451, 2008, A1. Location in patent: Page/Page column 47
[2] Patent: WO2014/170020, 2014, A1. Location in patent: Page/Page column 50
[3] Patent: US2009/156590, 2009, A1. Location in patent: Page/Page column 67; 69; 70
[4] Patent: US2012/28984, 2012, A1. Location in patent: Page/Page column 3
[5] Patent: WO2014/202580, 2014, A1. Location in patent: Page/Page column 164
