Tributylphosphine → 4-(4-Chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline

Participants

Reaction Steps

4-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (5.0 g, 15.6 mmol) was suspended in dichloromethane (150 ml) and tributylphosphine (11.1 ml, 44.6 mmol) was added followed by stirring at ambient temperature for 30 minutes. To this mixture was added 3-(1,1-dioxothiomorpholino)-1-propanol (4.2 g, 21.8 mmol) followed by the addition of 1,1′-(azodicarbonyl)dipiperidine (11.7 g, 46.4 mmol) in portions. The mixture was stirred at ambient temperature overnight then diluted with ether (300 ml) and the precipitate was removed by filtration. The residue was chromatographed on silica eluting with dichloromethane and methanol (95/5). The relevant fractions were combined and evaporated to give a solid which was triturated with ethyl acetate filtered and dried to give 4-(4-chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline (5.4 g, 70%). This was used without further purification in the next step.

Provenance & Evidence