Acetone → 4-fluoro-1H-indazol-3-amine

HRID 1808573Notes

Reaction equation

F[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].O.[NH2:12][NH2:13].CC(C)=O>C(O)C>[F:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]2[C:3]=1[C:4]([NH2:5])=[N:12][NH:13]2

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 2,6-difluorobenzonitrile (3 g, 21.6 mmol) in anhydrous ethanol (50 mL) was added hydrazine hydrate (4.18 mL, 86 mmol). The reaction was heated at 90° C. under nitrogen for 4 hours. Reaction mixture was cooled to room temperature, treated with acetone (20 mL) and left to stand for 18 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 (4.58 g), which was absorbed onto Florisil (60-100 mesh), applied to a 100 g silica SPE cartridge and purified on a Flashmaster II using a 0-10% methanol in dichloromethane gradient over 60 min. Fractions 48-57 were combined and the solvent was evaporated in-vacuo to yield the title compound as a brown solid (3.08 g, 94%). LCMS (System B) RT=1.38 min, ES+ve m/z 152 (M+H)+.

Workup

customReaction mixture
temperaturewas cooled to room temperature
waitleft
customThe mixture was evaporated in-vacuo
customto yield an orange/brown solid which
customwas partitioned between saturated aqueous sodium hydrogen carbonate solution and dichloromethane
customevaporated in-vacuo

Sources & evidence

ORD record: ord-c93c3b8cb4944f8b86a86808d5113f0f
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357716B2

Reaction notes

Loading…