855996-64-4Relevant academic research and scientific papers
Two Routes to 4-Fluorobenzisoxazol-3-one in the Synthesis of a 5-HT4 Partial Agonist
Widlicka, Daniel W.,Murray, John C.,Coffman, Karen J.,Xiao, Chunguang,Brodney, Michael A.,Rainville, Joseph P.,Samas, Brian
, p. 233 - 241 (2016/03/04)
A potent 5-HT4 partial agonist, 1 (PF-04995274), targeted for the treatment of Alzheimer's disease and cognitive impairment, has been prepared on a multi-kilogram scale. The initial synthetic route, that proceeded through a 4-substituted 3-hydroxybenzisoxazole core, gave an undesired benzoxazolinone through a Lossen-type rearrangement. Route scouting led to two new robust routes to the desired 4-substituted core. Process development led to the efficient assembly of the API on a pilot plant scale under process-friendly conditions with enhanced throughput. In addition, crystallization of a hemicitrate salt of the API with pharmaceutically beneficial properties was developed to enable progression of clinical studies.
(R)-4-((4-((4-(TETRAHYDROFURAN-3-YLOXY)BENZO[D]ISOXAZOL-3-YLOXY)METHYL)PIPERIDIN-1-YL)METHYL)TETRAHYDRO-2H-PYRAN-4-OL, A PARTIAL AGONIST OF 5-HT4 RECEPTORS
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Page/Page column 25-26, (2011/09/19)
(R)-4-((4-((4-(tetrahydrofuran-3-yloxy)benzo[d]isoxazol-3- yloxy)methyl)piperidin-1-yl)methyl)tetrahydro-2H-pyran-4-ol and its use in treating neurodegenerative disorders, is described herein.
