Cyclopenta[g]quinazolinone-based inhibitors of thymidylate synthase targeting α-folate receptor overexpressing tumours: synthetic approaches to 4-{N-[(6RS)-2-hydroxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benz

An advanced intermediate for the synthesis of cyclopenta[g]quinazolinone-based antifolates such as (6RS)-CB300945 was prepared by a convergent methodology. The oxo-functionality required for the formation of the C-6–N-10 bond in 4 was introduced in the initial steps of the synthesis, then the tricyclic ring was constructed and finally the propargyl group was introduced using the (propargyl)Co2(CO)6+ complex without the need to protect the N-3–H or 2-hydroxymethyl functionalities.