Diethyl Ether → HCID 21717238, compound

Participants

Reaction Steps

A solution of 5-acetyloxindole (272 mg, 1.56 mmol), (EP 0155828 A2), in DMF (1.5 ml) was added dropwise to a suspension of sodium hydride (62 mg, 1.56 mmol, prewashed with hexane) in DMF (3 ml) and, the mixture stirred for 30 minutes at ambient temperature. 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (175 mg, 0.52 mmol), (prepared as described for the starting material in Example 5), was added and the mixture was heated at 50° C. for 1.5 hours. The mixture was poured into a mixture of ether (30 ml), ethyl acetate (30 ml) and water (50 ml). The aqueous layer was separated and adjusted to pH7.8 with 2M hydrochloric acid and extracted with methylene chloride. The organic extracts were washed with water, brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (90/10). The purified solid was dissolved in methylene chloride/methanol and 7M ethanolic hydrogen chloride (1.5 ml) was added. The volatiles were removed by evaporation, the residue collected and dried under vacuum to give 4-(5-acetyloxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (135 mg, 48%).

Provenance & Evidence