Discovery of an Azabicyclo[2.1.1]hexane Piperazinium Salt and Its Application in Medicinal Chemistry via a Rearrangement.

Autor:	He C; Small Molecule Drug Discovery, Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States., Ba X; Small Molecule Drug Discovery, Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States., Shunatona HP; Small Molecule Drug Discovery, Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States., Edwards JT; Small Molecule Drug Discovery, Bristol Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States., Li YX; Small Molecule Drug Discovery, Bristol Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States., Keller TM; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08901, United States., Sommer RD; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08901, United States., Zapf CW; Small Molecule Drug Discovery, Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States., Mortensen DS; Small Molecule Drug Discovery, Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States.
Jazyk:	angličtina
Zdroj:	Organic letters [Org Lett] 2024 Jun 28; Vol. 26 (25), pp. 5318-5322. Date of Electronic Publication: 2024 Jun 18.
DOI:	10.1021/acs.orglett.4c01696
Abstrakt:	Herein we report the discovery of an azabicyclo[2.1.1]hexane piperazinium methanesulfonate salt from an unexpected rearrangement reaction in the preparation of ligand-directed degraders (LDDs). This bench-stable compound was found to be a versatile electrophile in a ring-opening reaction with various types of nucleophiles. Its utility as a versatile medicinal chemistry building block is further demonstrated in the synthesis of an LDD compound targeting degradation of the androgen receptor.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu