Alternative Routes to the Triazolopyrazine Core
A route permitting more late-stage diversification of the core would involve synthesis of a halogenated core that could be subjected to cross-coupling or nucleophilic displacement. Two such routes are shown below.
Preliminary progress towards both has been made by Tom Macdonald (link to Honours thesis coming). The first steps (acid-mediated cyclizations) have been successfully carried out for Halogenation Routes 1 and 2. The bromination step in Route 1 has reportedly been carried out (we lack the experimental write-up) and the halogenation in Route 2 was reportedly carried out in 58% yield (most recent lab book entry of presumably different attempt, more recent attempt by Alice). In 2016, Haochuan Mao completed a synthesis of the chloro-bromo compound, including securing its crystal structure, building on earlier work by Tianyi Zheng. A Haverford College superlab project also looked into this route. This chemistry is the subject of Synthetic Branch Project. It has also been looked at by Jasper Tyler (Sydney Uni) and Cohan (Griffith Uni) and Marat Korsik (Sydney Uni). To Do: The old synthetic branch page needs to be folded into this Github wiki. Comment to this effect.