Transition-Metal-Free Synthesis of a Densely Functionalized Benzodioxole Intermediate toward Lotiglipron

被引：0

作者：

Wang, Jimmy ^{[1
]}

Clarke, James ^{[1
]}

Badland, Matthew ^{[1
]}

Broadbelt, Brian ^{[2
]}

Dow, Louise F. ^{[2
]}

Fenton, Harriet A. M. ^{[1
]}

Laity, Daniel A. ^{[1
]}

Mathew, Jinu S. ^{[1
]}

Rose, Emily K. ^{[1
]}

Tamosiunaite, Neringa ^{[2
]}

Twiddle, Steven J. R. ^{[1
]}

Walton, Robert ^{[1
]}

机构：

[1] Pfizer R&D UK Ltd, Sandwich CT13 9NJ, Kent, England

[2] Concept Life Sci, Sandwich CT13 9NJ, Kent, England

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2024年 / 28卷 / 04期

关键词：

benzodioxole; lotiglipron; transition metalfree; alkylation; pyridine; KETONES;

D O I：

10.1021/acs.oprd.3c00472

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A decagram-scale preparation of the key intermediate (+/-)-2-(4-bromo-2-methylbenzo[d][1,3]dioxol-2-yl)-5-chloropyridine is described. Key steps involve a double nucleophilic substitution of 3-bromocatechol with methyl 2,2-dichloropropanoate, use of a Weinreb amide to facilitate the formation of a ketone from a carboxylic acid, and de novo construction of a substituted chloropyridine from a vinamidinium salt. Process developments enabled isolation of multigram quantities of final product in 34% yield after 5 steps and no chromatography.

引用

页码：1078 / 1082

页数：5

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