Scheme 1. Synthesis of 7-Deaza (N)-Methanocarba 5′-Esters.

Reagents and conditions: (i) TIPSCl, NaH, THF, 0 °C; (ii) 2,2,6,6-tetramethylpiperdine, n-BuLi, Bu₃SnCl, THF, −78 °C; (iii) I₂, THF, rt; (iv) TBAF, THF, 0 °C to rt; (v) 7-deaza-2-iodo-6-chloro-purine, Ph₃P, DIAD, THF, rt; (vi) MeNH₂·HCl, Et₃N, MeOH, rt; (vii) 2-chloro or 2-bromo-5-ethynylthiophene, Pd(Ph₃P)₂Cl₂, CuI, Et₃N, DMF, rt; and (viii) 10% TFA, MeOH, 70 °C.