N-(3-Aminopropyl)morpholine → 4-(4-chloro-2-fluoroanilino)-7-methoxy-6-(N-[3-morpholinopropyl]carbamoyl)quinoline

Participants

Reaction Steps

3-Morpholinopropylamine (290 mg, 2 mmol) was added to a solution of 6-carboxy-4-(4-chloro-2-fluoroanilino)-7-methoxyquinoline (200 mg, 0.5 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (191 mg, 1 mmol) and 1-hydroybenzotriazole hydrate (135 mg, 1 mmol) in DMF (15 ml). The mixture was stirred at ambient temperature for 2 hours. The solution was partitioned between water (100 ml) and methylene chloride. The organic layer was washed with brine and dried by passing through phase separating paper. The solvent was removed by evaporation and the crude product was purified by flash chromatography eluting with methylene chloride/methanol (99/1 increasing to 90/10). The pure fractions were combined and the solvent was removed by evaporation. The remaining oil was dissolved in methanol and an ethereal solution of hydrogen chloride was added. The solvent was removed by evaporation and the solid was dried overnight in a vacuum 1 oven at 40° C. to give 4-(4-chloro-2-fluoroanilino)-7-methoxy-6-(N-[3-morpholinopropyl]carbamoyl)quinoline (95 mg, 33%).

Provenance & Evidence