Judicious application of allyl protecting groups for the synthesis of 2-morpholin-4-yl-4-oxo-4H-chromen-8-yl triflate, a key precursor of DNA-dependent protein kinase inhibitors.
[Structure: see text] 2-morpholin-4-yl-4-oxo-4H-chromen-8-yl 2,2,2-trifluoromethanesulfonate is a key intermediate for the synthesis of the DNA-dependent protein kinase (DNA-PK) inhibitor 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441). Two improved methods for the synthesis of this triflate have been developed: (A) in 35% overall yield, through modification of the published route, and (B) in 15% overall yield, by a new route employing a Baker-Venkataraman rearrangement to enable generation of the chromenone scaffold. Both syntheses depend on the judicious use of allyl protecting groups.
Aristegui
Sonsoles Rodriguez
SR
Northern Institute for Cancer Research, School of Natural Sciences - Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.
El-Murr
Marine Desage
MD
Golding
Bernard T
BT
Griffin
Roger J
RJ
Hardcastle
Ian R
IR
D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors*; D008698:Mesylates / Q000138:chemical synthesis* / Q000494:pharmacology; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000737:chemistry*
C522875:2-morpholin-4-yl-4-oxo-4H-chromen-8-yl triflate; D001578:Benzopyrans; D008698:Mesylates; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D051747:DNA-Activated Protein Kinase