An SAR driven approach led to the discovery of a potent 5-HT4 receptor partial agonist, PF-4995274, as a potential treatment for Alzheimer's disease. Initial attempts to generate the hydroxybenzisoxazole 1  on a multi-gram scale were hampered by an unexpected rearrangement to benzoxazolinone 2 . The rearrangement was suppressed by switching from an electron donating to an electron withdrawing ortho-substituent. This key change along with further process optimization enabled a highly efficient synthesis of kilogram quantities of API.

Enabling the bulk synthesis of 5-HT<sub>4</sub> partial agonist, PF-4995274

248th National Meeting (2014)

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Enabling the bulk synthesis of 5-HT4 partial agonist, PF-4995274

Enabling the bulk synthesis of 5-HT₄ partial agonist, PF-4995274