Efficient synthesis of tert-butyl 3-cyano-3-cyclopropyl-2-oxopyrrolidine-4-carboxylates: Highly functionalized 2-pyrrolidinone enabling access to novel macrocyclic Tyk2 inhibitors.

Autor: Sasaki Y; Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑8555, Japan. Electronic address: yusuke.sasaki@takeda.com., Tokuhara H; Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑8555, Japan., Ohba Y; Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑8555, Japan., Okabe A; Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑8555, Japan., Nakayama M; Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑8555, Japan., Nakagawa H; Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑8555, Japan., Skene R; Takeda California, Inc., 10410 Science Center Drive, San Diego, CA 92121, United States., Hoffman I; Takeda California, Inc., 10410 Science Center Drive, San Diego, CA 92121, United States., Zou H; Takeda California, Inc., 10410 Science Center Drive, San Diego, CA 92121, United States., Yoshida M; Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26‑1, Muraoka‑Higashi 2‑chome, Fujisawa, Kanagawa 251‑8555, Japan.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Mar 01; Vol. 30 (5), pp. 126963. Date of Electronic Publication: 2020 Jan 13.
DOI: 10.1016/j.bmcl.2020.126963
Abstrakt: Herein we report an efficient method for the synthesis of a highly functionalized 2-pyrrolidinone, tert-butyl 3-cyano-3-cyclopropyl-2-oxopyrrolidine-4-carboxylate, from readily available starting materials. Utility of this compound was demonstrated in the synthesis of a novel series of macrocyclic Tyk2 inhibitors, leading to the identification of a potent and selective macrocyclic Tyk2 inhibitor (26).
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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