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Development and Scale-Up of an Optimized Route to the Pyridazin-3-one Histamine H3 Receptor Antagonist CEP-32215

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journal contribution
posted on 19.02.2016, 08:47 by Yi Wang, Katrin Przyuski, Renee C. Roemmele, Robert L. Hudkins, Roger P. Bakale
The evolution of the process to prepare CEP-32215, 3-(1′-cyclobutylspiro­[4H-1,3-benzodioxine-2,4′-piperidine]-6-yl)-5,5-dimethyl-1,4-dihydropyridazine-6-one, is presented. Two routes detailing preparation of supplies for biological screening are discussed along with the optimized fit-for-purpose process used to prepare several hundred grams for preclinical testing. Details on the development of the formation of the key spiroketal moiety are presented along with the discovery of a novel Suzuki coupling approach for synthesis of the backbone of the molecule.