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. Author manuscript; available in PMC: 2015 Feb 1.
Published in final edited form as: Antiviral Res. 2013 Nov 23;102:119–147. doi: 10.1016/j.antiviral.2013.11.008

Scheme 10.

Scheme 10

Synthesis of 4′-azido-2′-deoxy-2′-methyl cytidine (TMC649128). Reagents and conditions: (a) bis(trimethylsilyl)uracil, SnCl4, CH3CN, r.t., 20 h, 96%; (b) NH3, CH3OH, 0–4 °C, 2 days, >99%; (c) TIPDSCl2, imidazole, DMF, r.t., 2 h, 65%; (d) ClCOCO2Me, DMAP, CH3CN, r.t., 1 h; (e) n-Bu3SnH, AIBN, toluene, reflux, 2 h, 97% (β/α 93:7, de 86%) over two steps; (f) TBAF/THF, r.t., 1 h, >99% (β/α 93:7); (g) I2, PPh3, imidazole, THF, 76%; (h) NaOMe, MeOH, 75%; (i) i. I2, NMO, Bn(Et)3NN3; ii. BzCl, NMP, DMAP, THF, 81% over 2 steps; (j) m-CPBA, (NH4)2SO4, DCM, 68%; (k) i. pyridine, 2-chlorophenyldichlorophosphate, 1-H-tetrazole; ii. dioxane, NH3; iii. NH3, MeOH, 61% over 3 steps; (l) i-PrCOCl, TEA, DCM, r.t., >99%.