Phosphorus oxychloride → 3-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloro-8-fluoroquinoline

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(4-(1H-pyrazol-1-yl)benzyl)malonic acid (4 g, 15.37 mmol, Intermediate 6: step b) and 4-bromo-2-fluoroaniline (2.7 g, 13.973 mmol) in POCl3 (20 mL) was heated at 105° C. for 3 hours, cooled to room temperature and evaporated in vacuo to remove excess POCl3. The residue was poured into ice H2O and treated with aqueous NH4OH to pH 8-9 (temperature of the aqueous mixture was kept cold during addition). The precipitates were collected, rinsed with H2O and dried under reduced pressure. The solids were diluted with DCM and insoluble solids filtered off. The filtrate was evaporated to dryness to provide product as a tan solid.

Provenance & Evidence