Flow synthesis of ethyl isocyanoacetate enabling the telescoped synthesis of 1,2,4-triazoles and pyrrolo-[1,2-c]pyrimidines.
The efficient flow synthesis of important heterocyclic building blocks based on the 1,2,4-triazole and pyrrolo[1,2-c]pyrimidine scaffold has been achieved. Crucially, a telescoped continuous flow process was developed based on the reaction of N-formylglycine with triphosgene to deliver a stream of ethyl isocyanoacetate in situ, which subsequently yielded the desired heterocyclic entities in a telescoped reaction. Additionally, the functionalisation of the pyrrolo[1,2-c]pyrimidine core via subsequent SEAr reactions was studied revealing insight into a 'halogen dance' phenomenon associated with these medicinally relevant architectures.
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. i.r.baxendale@durham.ac.uk.
Marcus
M
Baumann
Antonio M
AM
Rodriguez Garcia
Ian R
IR
Baxendale
D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic / Q000295:instrumentation / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D010705:Phosgene / Q000031:analogs & derivatives / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D014230:Triazoles / Q000138:chemical synthesis*
D000085:Acetates; D009570:Nitriles; D011743:Pyrimidines; D014230:Triazoles; D010705:Phosgene; C045575:1,2,4-triazole; C111044:bis(trichloromethyl) carbonate; C030986:pyrimidine