Acetone → 3-Amino-4-chloroindazole

Temperature

90 °C

To a solution of 2-chloro-6-fluorobenzonitrile (ABCR) (3 g, 19 mmol) in anhydrous ethanol (50 mL) was added hydrazine hydrate (3.74 mL, 77 mmol). The reaction was heated at 90° C. under a nitrogen for 3.5 hours. The reaction mixture was cooled to room temperature, treated with acetone (20 mL) and left to stand for 19 hours. The mixture was evaporated in-vacuo to yield an orange/brown solid, which was partitioned between saturated aqueous sodium hydrogen carbonate solution and dichloromethane. The organic layer was passed through a hydrophobic frit and evaporated in-vacuo to yield a brown solid, which was absorbed onto Florisil (60-100 mesh), applied to a 100 g silica SPE cartridge and purified by chromatography on Flashmaster II using a 0-10% methanol in dichloromethane gradient over 60 min. Fractions 24-29 were combined and the solvent was evaporated in-vacuo to yield the title compound as a yellow solid (2.14 g, 66%) LCMS (System B) RT=1.58 min, ES+ve m/z 168 (M+H)+.

1. temperatureThe reaction mixture was cooled to room temperature
2. waitleft
3. customThe mixture was evaporated in-vacuo
4. customto yield an orange/brown solid, which
5. customwas partitioned between saturated aqueous sodium hydrogen carbonate solution and dichloromethane
6. customevaporated in-vacuo
7. customto yield a brown solid, which
8. customwas absorbed onto Florisil (60-100 mesh)
9. custompurified by chromatography on Flashmaster II
10. customover 60 min
11. customthe solvent was evaporated in-vacuo

ORD record

ord-f22de010250849178ffde31be4b9a2a6

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304446B2