Scheme 10.
Synthesis of the thymine Ara-FHNA phosphoramidite. (a) i) trifluoromethanesulfonic anhydride, pyridine, ii) CsF, tert-butanol; (b) i) Amberlite IR-120-H, 1,4-dioxane, water, ii) acetic anhydride, pyridine; (c) i) 33% HBr in acetic acid, dichloromethane, ii) tributyltin hydride, 2,2′-azobis(2-methylpropionitrile), toluene; (d) i) K2CO3, methanol, ii) benzaldehyde dimethyl acetal, p-toluenesulfonic acid, DMF; (e) i) trifluoromethanesulfonic anhydride, dichloromethane, pyridine, ii) N3-benzyloxymethylthymine, 1,8-diazabicyclo[5.4.0]undec-7-ene, dimethyl sulfoxide; (f) H2, Pd(OH)2/C, methanol; (g) DMTCI, pyridine; (h) P(NiPr2)2(OCE), 1H-tetrazole, NMI, DMF. Bom = benzyloxymethyl. Adapted from [221].