反应详情

温度

15 °C

6-Chloro-4-iodo-1H-indazole (1.0 eq., 1 wt, 50 g), sodium hydroxide (2.25 eq., 0.324 wt, 16.16 g) and tetrabutylammonium hydrogensulphate (0.05 eq., 0.061 wt, 3.05 g) are stirred in THF (9.5 vols, 475 ml) at 20±3° C. under a nitrogen atmosphere for 1 hr. The mixture is cooled to 15±3° C. and benzenesulfonyl chloride (1.10 eq., 0.51 vols, 25.5 ml) was added dropwise over 20 mins maintaining the reaction temperature at <25° C. and is washed in with THF (0.5 vols, 25 ml). The resulting mixture is then stirred under a nitrogen atmosphere at 20±3° C. for at least 1 hr before checking for completion by HPLC. The reaction mixture is then added to 0.25 M hydrochloric acid solution (18 vols, 900 ml) cooled to 0±3° C. over 15 minutes maintaining the temperature of the aqueous suspension at <20° C. This is washed in with 0.25M hydrochloric acid solution (2 vols, 100 ml). The resulting orange suspension is then stirred at 2±3° C. for at least 1 hr. The solid is filtered, washed with water (2×3 vols, 2×150 ml) and sucked dry for 20 mins, then dried under high vacuum at 40° C. (±3° C.) to constant probe temperature to afford 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole as an orange solid.

1. temperaturemaintaining the reaction temperature at <25° C.
2. washis washed in with THF (0.5 vols, 25 ml)
3. additionThe reaction mixture is then added to 0.25 M hydrochloric acid solution (18 vols, 900 ml)
4. temperaturecooled to 0±3° C. over 15 minutes
5. temperaturemaintaining the temperature of the aqueous suspension at <20° C
6. washThis is washed in with 0.25M hydrochloric acid solution (2 vols, 100 ml)
7. stirringThe resulting orange suspension is then stirred at 2±3° C. for at least 1 hr
8. filtrationThe solid is filtered
9. washwashed with water (2×3 vols, 2×150 ml)
10. customsucked dry for 20 mins
11. customdried under high vacuum at 40° C. (±3° C.) to constant probe temperature