2. Academic Validation
  3. A Concise Enantioselective Synthesis of Fluorinated Pyrazolo-Piperidine GSK3901383A Enabled by an Organocatalytic Aza-Michael Addition

A Concise Enantioselective Synthesis of Fluorinated Pyrazolo-Piperidine GSK3901383A Enabled by an Organocatalytic Aza-Michael Addition

  • Org Lett. 2024 Mar 1;26(8):1533-1538. doi: 10.1021/acs.orglett.3c03694.
Benedict Barron 1,  Colin Edge 2,  Sabine Fenner 1,  Harry Shrives 3,  Steven Sollis 3,  Matthew Whiting 1,  Damien Valette 1
Affiliations

Affiliations

  • 1 Drug Substance Development, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
  • 2 Computational Chemistry, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
  • 3 Medicinal Chemistry, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
PMID: 38363757 DOI: 10.1021/acs.orglett.3c03694
Abstract

A highly enantioselective organocatalytic aza-Michael addition of 4-nitro-pyrazole to ethyl (E)-2,2-difluoro-5-oxopent-3-enoate has been developed. This reaction enabled a concise, four-step, stereoselective synthesis of highly functionalized 3,3-difluoro-4-pyrazolo-piperidine GSK3901383A, a key intermediate for the synthesis of a leucine-rich repeat kinase 2 inhibitor API. Computational analysis provided insight into the steric requirements of the catalytic system, enabling rational selection of a highly selective catalyst.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z