title: Efficient synthesis of exo-N-carbamoyl nucleosides: application to the synthesis of phosphoramidate prodrugs.
abstract: An efficient protection protocol for the 6-exo-amino group of purine nucleosides with various chloroformates was developed utilizing N-methylimidazole (NMI). The reaction of an exo-N(6)-group of adenosine analogue 1 with alkyl/and aryl chloroformates under optimized conditions provided the N(6)-carbamoyl adenosines (2a-j) in good to excellent yields. The reaction of N(6)-Cbz-protected nucleosides (5a-c) with phenyl phosphoryl chloride (7) using t-BuMgCl followed by catalytic hydrogenation afforded the corresponding phosphoramidate pronucleotides (8a-c) in excellent yield.
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine , and Veterans Affairs Medical Center, Decatur, Georgia 30033, United States, and RFS Pharma, LLC , 1860 Montreal Road, Tucker, Georgia 30084, United States.
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Cho
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Coats
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D007093:Imidazoles / Q000737:chemistry; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D011684:Purine Nucleosides / Q000737:chemistry
chemical_list: D000577:Amides; D007093:Imidazoles; D009705:Nucleosides; D010756:Phosphoric Acids; D011355:Prodrugs; D011684:Purine Nucleosides; D000249:Adenosine Monophosphate; C011067:phosphoramidic acid; C018100:1-methylimidazole