Modular Synthesis of 3,6-Disubstituted-1,2,4-triazines via the Cyclodehydration of β-Keto-N-acylsulfonarnides with Hydrazine Salts

被引：11

作者：

Dowling, Matthew S. ^{[1
]}

Jiao, Wenhua ^{[1
]}

Hou, Jie ^{[2
]}

Jiang, Yuchun ^{[2
]}

Gong, Shangsheng ^{[2
]}

机构：

[1] Pfizer Inc, Med Design, Eastern Point Rd, Groton, CT 06340 USA

[2] WuXi AppTec, 288 Fute Zhong Rd, Shanghai 200131, Peoples R China

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2018年 / 83卷 / 07期

关键词：

AS-TRIAZINE DERIVATIVES; DIELS-ALDER REACTION; SUBSTITUTED 1,2,4-TRIAZINES; ACID; DISCOVERY; ANALOGS; ACCESS; RING;

D O I：

10.1021/acs.joc.8b00254

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A straightforward method for preparing 3,6-disubstituted-1,2,4-triazines through a redox-efficient cyclo-dehydration of beta-keto-N-acylsulfonamides with hydrazine salts is described. Two approaches for synthesizing the requisite beta-keto-N-acylsulfonarnides are presented, which allow for the late stage incorporation of either the C3 or C6 substituent in a flexible manner from acid chlorides or alpha-bromoketones, respectively. The scope of this methodology includes primary and secondary sp(3)-linked substituents at both the C3 and C6 positions, and the mild reaction conditions tolerate a variety of sensitive functionalities.

引用

页码：4229 / 4238

页数：10