The SHMS 11 GeV/c spectrometer in Hall C at Jefferson Lab

Ali, S; Ahmidouch, A; Ambrose, GR; Asaturyan, A (ORCID:000000028105913X); Gayoso, C Ayerbe (ORCID:0000000186405380); Benesch, J; Berdnikov, V (ORCID:0000000316034320); Bhatt, H (ORCID:0000000300875387); Bhetuwal, D; Biswas, D (ORCID:000900011427979X); Brindza, P; Bukhari, M; Burton, M; Carlini, R; Carmignotto, M (ORCID:0000000203219521); Christy, ME; Cotton, C; Crafts, J; Day, D (ORCID:0000000171268934); Danagoulian, S; Dittmann, A (ORCID:0000000161576722); Dongwi, DH; Duran, B; Dutta, D; Ent, R; Fenker, H; Fowler, M; Gaskell, D (ORCID:0000000154634867); Hamdi, A (ORCID:0000000170999452); Heinrich, N (ORCID:0009000587209329); Henry, W; Hlavin, N; Horn, T (ORCID:0000000319259541); Huber, GM (ORCID:0000000256581065); Ilieva, Y (ORCID:0000000335730057); Jarrell, J; Jia, S; Jones, MK (ORCID:0000000270896311); Junaid, M (ORCID:0000000258534326); Kabir, ML; Kalantarians, N; Karki, A (ORCID:0000000176502646); Kay, SJD (ORCID:0000000288553034); Keppel, CE; Kumar, V; Lassiter, S; Li, WB (ORCID:0000000281088045); Mack, D; Malace, S; McMahon, J; Mkrtchyan, A; Mkrtchyan, H (ORCID:0000000343589380); Monaghan, P; Morean, C (ORCID:0000000155884841); Nadel-Turonski, P; Niculescu, G; Niculescu, MI (ORCID:0000000345267457); Nadeeshani, A (ORCID:0000000257368274); Pooser, E; Ramos, A; Reinhold, J; Sawatzky, B (ORCID:0000000256370348); Szumila-Vance, H (ORCID:0000000325484016); Tadevosyan, V (ORCID:0000000161328999); Trotta, RL (ORCID:0000000281936139); Usman, A; Yero, C (ORCID:0000000328227373); Yurov, M (ORCID:0000000287603116); Zhamkochyan, S; Wood, SA (ORCID:0000000219095287); Zhang, J

doi:10.1016/j.nima.2025.171070

Small molecule solutions to many contemporary societal challenges await discovery, but the artisanal and manual process via which this class of chemical matter is typically accessed limits the discovery of new functions. Automated assembly of (N‐methyl iminodiacetic acid) MIDA or (tetramethyl N‐methyl iminodiacetic acid) TIDA boronate building blocks via iterative C─C bond formation, an approach we call “block chemistry”, alternatively enables generalized and automated preparation of many different types of small molecules in a modular fashion. But in its current form, this engine cannot also leverage nitrogen atoms as iteration handles. Here, we disclose a new iteration‐enabling group, CbzT (p‐TIDA boronate‐substituted carboxybenzyl), that reversibly attenuates the reactivity of nitrogen atoms and enables generalized catch‐and‐release purification. CbzT is leveraged to achieve the automated modular synthesis of Imatinib (Gleevec), an archetypical clinically approved kinase inhibitor, in which building blocks are iteratively linked by both N─C and C─C bonds. This work substantially expands the types of small molecules that can be iteratively assembled in an automated modular fashion. It also advances the concept of intentionally developing chemistry that machines can do.

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