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

被引：12

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

共 46 条

[21]

KONNO S, 1986, HETEROCYCLES, V24, P1243

[22] Facile synthesis of 6-aryl-3-pyridyl-1,2,4-triazines as a key step toward highly fluorescent 5-substituted bipyridines and their Zn(II) and Ru(II) complexes [J].

Kozhevnikov, Valery N. ;

Shabunina, Olga V. ;

Kopchuk, Dmitry S. ;

Ustinova, Maria M. ;

Koenig, Burkhard ;

Kozhevnikov, Dmitry N. .

TETRAHEDRON, 2008, 64 (37) :8963-8973

[23] An efficient route to 5-(hetero)aryl-2,4′- and 2,2′-bipyridines through readily available 3-pyridyl-1,2,4-triazines [J].

Kozhevnikov, VN ;

Kozhevnikov, DN ;

Shabunina, OV ;

Rusinov, VL ;

Chupakhin, ON .

TETRAHEDRON LETTERS, 2005, 46 (11) :1791-1793

[24] Tandem oxidation processes for the regioselective preparation of 5-substituted and 6-substituted 1,2,4-triazines [J].

Laphookhieo, Surat ;

Jones, Stuart ;

Raw, Steven A. ;

Sainz, Yolanda Fernandez ;

Taylor, Richard J. K. .

TETRAHEDRON LETTERS, 2006, 47 (23) :3865-3870

[25] Sequential Michael Addition and Enamine-Promoted Inverse Electron Demanding Diels-Alder Reaction upon 3-Vinyl-1,2,4-triazine Platforms [J].

Lorion, Magali ;

Guillaumet, Gerald ;

Briere, Jean-Francois ;

Suzenet, Franck .

ORGANIC LETTERS, 2015, 17 (12) :3154-3157

[26] Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success [J].

Lovering, Frank ;

Bikker, Jack ;

Humblet, Christine .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (21) :6752-6756

[27] Zn-catalyzed hydrohydrazination of propargylamides with BocNHNH2: a novel entry into the 1,2,4-triazine core [J].

Lukin, Alexey ;

Vedekhina, Tatiana ;

Tovpeko, Dmitry ;

Zhurilo, Nikolay ;

Krasavin, Mikhail .

RSC ADVANCES, 2016, 6 (63) :57956-57959

[28] Unexpected O-H Insertion of Rhodium-Azavinylcarbenes with N-Acylhydrazones: Divergent Synthesis of 3,6-Disubstituted- and 3,5 6-Trisubstituted-1,2,4-Triazines [J].

Meng, Jiang ;

Wen, Min ;

Zhang, Shiwei ;

Pan, Peiwen ;

Yu, Xingxin ;

Deng, Wei-Ping .

JOURNAL OF ORGANIC CHEMISTRY, 2017, 82 (03) :1676-1687

[29] UBER DIE ROTEN ANILE - DARSTELLUNG VON ALPHA-(P-DIALKYLAMINOPHENYLIMINO)-BETA-KETO-PHTHALIMIDO-ALKANCARBONSAURENITRILEN [J].

MICHALSKY, J .

JOURNAL FUR PRAKTISCHE CHEMIE, 1959, 8 (3-4) :186-198

[30]

O'ROURKE M, 1977, Journal of Medicinal Chemistry, V20, P723

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