title: 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.
abstract: [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.
authors.affiliation: Northern Institute for Cancer Research, School of Natural Sciences - Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.
authors.forename: Sonsoles Rodriguez
authors.initials: SR
authors.lastname: Aristegui
authors.forename: Marine Desage
authors.initials: MD
authors.lastname: El-Murr
authors.forename: Bernard T
authors.initials: BT
authors.lastname: Golding
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Griffin
authors.forename: Ian R
authors.initials: IR
authors.lastname: Hardcastle
mesh_terms: 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*
chemical_list: 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