Sodium hydride → HCID 21717279, compound

Participants

Reaction Steps

A solution of 5-methylsulphinyloxindole (303 mg, 1.55 mmol) in DMF (3.5 ml) was added to a suspension of sodium hydride (62 mg, 1.55 mmol, prewashed with hexane) in DMF (1.5 ml) and the mixture stirred for 30 minutes at ambient temperature. 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (175 mg, 0.51 mmol), (prepared as described for the starting material in Example 5), was added and the mixture was stirred for 1.5 hours at 50° C. and then partitioned between water and ether. The aqueous layer was adjusted to pH7-8 with 2M hydrochloric acid and the volatiles removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (9/1). The semi-purified solid was dissolved in dilute hydrochloric acid (pH2) and purified by reverse phase C18 chromatography eluting with methanol/dilute hydrochloric acid (pH2) (gradient from 0/100 to 30/70). The methanol was removed by evaporation, the aqueous residue was freeze dried to give 6-methoxy-4-(5-methylsulphinyloxindol-3-yl)-7-(3-morpholinopropoxy)quinazoline hydrochloride (80 mg, 27%).

Provenance & Evidence