Carbon−Carbon Bond-Forming Solid-Phase Reactions. Part II

Nucleophile Cleavable Linker Units

“…The reaction could be used for both the formation of carbon-carbon as well as carbon heteroatom bonds complementing the numerous palladium-based methodologies for carbon-carbon crosscoupling. [101] Recently, Cassel et al [102] have published a short report on the Nicholas reaction on the solid phase, involving the reaction of a polymer-bound alkynol 185 with aryl halides via a Sonogashira coupling, followed by treatment with dicobalt octacarbonyl and subsequent reaction with boron trifluoride in conjunction with oxygen or carbon nucleophiles (Scheme 3.46).…”

Solid‐Phase N‐Electrophilic Amination of 2‐Aminopyridines: Preparation of 2‐Substituted‐[1,2,4]triazolo[1,5‐a]pyridine Derivatives

“…As a result, an increasing number of pharmaceutically useful heterocyclic compounds have recently been prepared using solid-phase methodology [2]. A broad number of organic transformations have been adapted to solid-phase synthesis with excellent results, as documented by several reviews [3]. Nevertheless, there is still the need to introduce new reactions into the arsenal of solid-phase organic transformations to increase the synthetic potential of this methodology.…”

“…The polymerbound N-aminated pyridine (2) was then condensed with a wide variety of aldehydes (aliphatic aldehydes, substituted benzaldehydes, and heterocyclic carboxaldehydes), and subsequent cyclization and oxidation yielded polymerbound triazolo-pyridine derivatives (3). Cleavage from the resin was effected by treatment with Trifluoroacetic Acid (TFA) in Dichloromethane (DCM) (1 : 1) to afford the desired 2-substituted- [1,2,4]triazolo [1,5-a]pyridin-6/8-yl derivatives (4) in good purity and yields.…”

Solid-phase organic synthesis of heterocyclic compounds

“…Combinatorial and parallel synthetic methodologies provide the main driving force for the preparation of libraries for applications in the discovery of lead compounds and high-throughput medicinal chemistry within the pharmaceutical industry. [1][2][3] Many different formats of high-throughput chemistry are available and solid-phase organic synthesis (SPOS) plays a pivotal role allowing the convenient handling of large numbers of synthetic intermediates. 4,5) Since the combinatorial chemistry first appeared in the early 1990s, the way drugs are discovered has changed dramatically.…”