Process for the preparation of tubulin inhibitors

摘要

The present invention provides a process for the preparation of 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt and as a hydrated salt having the structural formula (I) wherein: R¹ is CF₃ or C₂F₅; R² is H or C₁-C₃ alkyl; n is an integer of 2, 3, or 4; X is Cl or Br; R³ and R⁴ are each independently H or C₁-C₃ alkyl; or R³ and R⁴ when optionally taken together with the nitrogen atom to which each is attached form a 4 to 6 membered saturated heterocyclic ring having 1-2 nitrogen atoms and 0-1 oxygen atoms or 0-1 sulfur atoms, and optionally substituted with R⁵; R⁵ is C₁-C₃ alkyl; wherein the dotted line is an optional bond.