1,4-Dioxa-8-azaspiro(4.5)decane → HCID 10218231, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[(2R)-oxiran-2-ylmethoxy]quinazoline (200 mg, 0.506 mmol), (prepared as described for the starting material in Example 48), and 1,4-dioxa-8-azaspiro[4.5]decane (195 μl, 1.52 mmol) in DMF (3 ml) was stirred at 70° C. under argon for 3 hours. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10). The fractions containing the expected product were combined and evaporated to dryness. The residue was triturated with diethyl ether, filtered and dried under vacuum to give 7-{(2R)-3-[(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)]-2-hydroxypropoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (190 mg, 70%).

Provenance & Evidence