Leaching resistance and robustness of the active sites. H-CCAT targets less than 20 ppm metal traces under both batch and continuous flow catalytic conditions, which is in the range of the admissible noble metal contamination in API synthesis. This ambitious target will be reached by using molecularly pre-designed active sites in which the strongly bonding ligands keep the metals (Pd, Ru, Ni, ..) well-fixed to the hybrid material.
Material robustness. Rather than classical polymers (e.g. polystyrene based ones) H-CCAT uses robust materials, with strong Si-C and Si-O-Si bonds in the hybrid silica, or with the particularly stable coordinative bonds in Zr4+ and Cr3+ MOF materials. These readily withstand temperatures ≥ 150°C, which is the required temperature for e.g. the dehydrogenative processes.
The academic partners are world-leading groups in the field of catalysis and nanoporous materials. This will allow to go well beyond the state-of-the-art and to achieve important breakthroughs. The (industrial) partners are key players in the value chain; this will decrease the time-to-market for the new catalysts and speed up adoption of the catalytic processes in pharmaceutical production.
Some of the key molecules for which J&J could use C-H activation technology include Rilpivirine in the first place, and also Ibrutinib and VX-787. All the key molecules are APIs with a massive societal and economic importance, with potentially 107-108 treatments per year worldwide for Rilpivirine and VX-787, or even more.
H-CCAT will overcome the main bottlenecks in current API production.
First, the catalysts of H-CCAT will reach much higher TON, because of their intrinsic resistance against deactivation; consequently, they can also be used at higher temperatures (e.g. for C-H/C-X coupling), which raises TOF. In fact, other factors than catalyst cost then start to dominate process economics, both regarding cost of goods and regarding cost of operation. In the synthesis of a typical API, overall costs are ~ equally split in goods and raw materials (50%) and operational costs (50%). These can be significantly reduced by reducing the cost of goods and reducing operational costs by reaching higher step economy and reducing the number of unit operations by making the process heterogeneous. Additionally, H-CCAT will reinforce its positive economic benefits through the minimisation of downtime of the plants and flexibilisation of the production (with respect to temporal planning).
Finally, H-CCAT will have several positive environmental impacts:
1) Synthesis via C-H/C-H coupling or C-H/C-X coupling will produce significantly less waste (halides, borates, …), or even no waste at all (for the C-H/C-H coupling under oxygen). 2) Efficient metal immobilization strongly reduces the production of metal-contaminated wastes (e.g. liquids), and also makes the APIs much safer for the patient to ingest;
3) Some of the more toxic intermediates can be avoided.
4) H-CCAT will devote specific efforts to realize flow, reducing the environmental impact of the synthesis.
5) Preference will be given to use less harmful reagents and solvents.
The positive environmental impacts will be demonstrated through an LCA assessment.
