Triethylamine → HCID 11604752, compound

Participants

Reaction Conditions

Reaction Steps

In a 50 mL-volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 2.00 g (6.3 mmol) of 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one, 1.19 g (7.6 mmol) of phosphorus oxychloride, 0.76 g (6.3 mmol) of triethylamine, and 8 mL of toluene in a nitrogen atmosphere. The mixture was then stirred at 70-80° C. for 3 hours. Subsequently, the mixture was cooled to room temperature, and 1.09 g (6.3 mmol) of 3-chloro-4-fluoroaniline and 6 mL of toluene were added. The resulting mixture was stirred at 110° C. for 10 hours, Further, the mixture was stirred at room temperature after addition of 8 mL of acetonitrile. After the reaction was complete, the precipitated crystalline product was collected by filtration, and washed with 5 mL of cooled acetonitrile. Subsequently, the crystalline product was placed in 16 mL of aqueous sodium hydroxide (1 mol/L), and the aqueous mixture was stirred for 4 hours at room temperature. The crystalline product was collected by filtration, washed with 50 mL of water and 5 mL of acetonitrile, and dried under reduced pressure, to give 2.28 g (isolated yield: 71%, purity 89% in terms of area percentage determined by high performance liquid chromatography) of 4-(3-chloro-4-fluoroanilino)-6-methoxy-7-(3-morpholinopropoxy)quinazoline as a sallowish crystalline product.

Provenance & Evidence