Ammonium Hydroxide → (3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

Participants

Reaction Conditions

Reaction Steps

A heterogeneous mixture of (4-amino-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone (1.0 g, 4.6 mmol, Intermediate 14: step c), 2-(4-(1H-pyrazol-1-yl)benzyl)malonic acid (1.3 g, 4.6 mmol, Intermediate 3: step b) and POCl3 (4.3 mL) was heated at 105° C. for 18 hours then cooled to room temperature. The mixture was poured into ice water and treated with aqueous NH4OH solution (kept adding ice during addition) to a basic pH 8-9. The aqueous layer was extracted with DCM, washed with a saturated aqueous solution of NaCl, dried (MgSO4) and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-100% EtOAc/DCM) to provide the title compound.

Provenance & Evidence