Stannous Chloride → 5-[(3,5-difluorobenzyl)oxy]-1H-indazol-3-amine

Participants

Reaction Steps

A solution of sodium nitrite (13 gr, 190 mmol) in water (15 mL) was added dropwise to a cooled (0° C.) mixture of 2-amino-5-[(3,5-difluorobenzyl)oxy]benzonitrile (42.9 g, 165 mmol) in 37% hydrochloric acid (340 mL). After 2 hours, the resulting reaction mixture was added over a period of 1 hour to a previously prepared cooled suspension of tin(II) chloride (250 gr, 1.32 mol) in 37% hydrochloric acid (286 mL) trying to keep the temperature below 10° C. After 1 hour, the resulting reaction mixture was diluted with water (400 mL) and 35% NaOH (735 mL) was added to obtain a pH value of 9-10. The reaction mixture was extracted with EtOAc (1 L) and washed with EtOAc (2×0.5 L). Collected organic phases were dried over sodium sulfate, filtered and evaporated to dryness. The crude residue was purified by chromatography on silica gel using dichloromethane/7M NH3 in MeOH 96:4 as the eluant, affording 34.7 g of the title compound (76% yield).

Provenance & Evidence