一步法合成1,2,4-三氮唑[3,4-i]嘌呤类化合物

doi:10.6023/cjoc202110007

有机化学 ›› 2022, Vol. 42 ›› Issue (5): 1551-1556.DOI: 10.6023/cjoc202110007 上一篇下一篇

研究简报

一步法合成1,2,4-三氮唑[3,4-i]嘌呤类化合物

楚治良^a, 陈晖娟^a, 单帅^a, 王晓娜^a, 高春芳^a, 渠桂荣^b, 刘忠于^a^,^*(), 郭海明^b^,^*()

a 中国人民解放军联勤保障部队第989医院河南洛阳 471031
b 河南师范大学化学化工学院河南新乡 453007

收稿日期:2021-10-08 修回日期:2022-01-26 发布日期:2022-02-10
通讯作者: 刘忠于, 郭海明
基金资助:
国家自然科学基金(U1604283); 国家科技重大专项(2014ZX09J14101-01A); 洛阳市科技计划医疗卫生(1720001A-8)

One-Step Synthesis of 1,2,4-Triazolo[3,4-i]purine Derivatives

Zhiliang Chu^a, Huijuan Chen^a, Shuai Shan^a, Xiaona Wang^a, Chunfang Gao^a, Guirong Qu^b, Zhongyu Liu^a(), Haiming Guo^b()

a The 989th Hospital of the Joint Logistics Support Force of Chinese People's Liberation Army, Luoyang, Henan 471031
b School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007

Received:2021-10-08 Revised:2022-01-26 Published:2022-02-10
Contact: Zhongyu Liu, Haiming Guo
Supported by:
National Natural Science Foundation of China(U1604283); National Science and Technology Major Project(2014ZX09J14101-01A); Medical and Health Project of Luoyang Science and Technology Plan(1720001A-8)

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摘要/Abstract

1,2,4-三氮唑[3,4-i]嘌呤类化合物是潜在的黄嘌呤氧化酶(XO)抑制剂, 有望用于痛风的治疗. 报道了一种一步合成1,2,4-三氮唑[3,4-i]嘌呤类化合物的新方法. 以6-肼基-N⁹-取代嘌呤和脂肪族一元羧酸为原料, 无水硫酸镁作除水剂, 合成了17个新化合物. 该方法操作简单, 无需使用其他催化剂和氧化剂, 且收率良好. 同时, 探讨了影响反应的因素, 为1,2,4-三氮唑[3,4-i]嘌呤类化合物研究奠定了基础.

关键词: 6-肼基-N⁹-取代嘌呤, 脂肪族一元羧酸, 1,2,4-三氮唑[3,4-i]嘌呤类化合物

1,2,4-Triazolo[3,4-i]purine derivatives are potential xanthine oxidase (XO) inhibitors and expected to be used in the treatment of gout. A new one-step method for the preparation of 1,2,4-triazolo[3,4-i]purine derivatives has been reported. Seventeen novel 1,2,4-triazolo[3,4-i]purine derivatives were synthesized with 6-hydrazinyl-N⁹-substituted purine and aliphatic monocarboxylic acid as starting materials and anhydrous magnesium sulfate as dehydrating agent. The method is easy to operate without using other catalysts and oxidants, and the yield is good. Meanwhile, the factors affecting the reaction were discussed, which laid a foundation for the study of 1,2,4-triazolo[3,4-i]purine compounds

Key words: 6-hydrazinyl-N⁹-substituted purine, aliphatic monocarboxylic acid, 1,2,4-triazolo[3,4-i]purine derivative

引用此文

楚治良, 陈晖娟, 单帅, 王晓娜, 高春芳, 渠桂荣, 刘忠于, 郭海明. 一步法合成1,2,4-三氮唑[3,4-i]嘌呤类化合物[J]. 有机化学, 2022, 42(5): 1551-1556.

Zhiliang Chu, Huijuan Chen, Shuai Shan, Xiaona Wang, Chunfang Gao, Guirong Qu, Zhongyu Liu, Haiming Guo. One-Step Synthesis of 1,2,4-Triazolo[3,4-i]purine Derivatives[J]. Chinese Journal of Organic Chemistry, 2022, 42(5): 1551-1556.

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图/表 5

图式1. 合成1,2,4-三氮唑[3,4-i]嘌呤类化合物的方法

Scheme 1. Method for the preparation of 1,2,4-triazolo[3,4- i]purine derivatives

图式2. 1,2,4-三氮唑[3,4-i]嘌呤类化合物的合成

Scheme 2. Synthesis of 1,2,4-triazolo[3,4-i]purine derivatives

Entry	Dehydrating agent (equiv.)	T/℃	Time/h	Isolated yield/%
1	None	120	24	46
2	MgSO₄ (1.0)	120	24	66
3	MgSO₄ (2.0)	120	24	89
4	MgSO₄ (4.0)	120	24	87
5	MgSO₄ (2.0)	100	24	36
6	MgSO₄ (2.0)	80	24	Trace
7	MgSO₄(2.0)	140	24	80
8	MgSO₄ (2.0)	120	36	83
9	4Å MS (2.0)	120	24	63
10	Na₂SO₄ (2.0)	120	24	50
11^b	None	120	24	0
12^c	MgSO₄ (2.0)	120	24	65
13^d	MgSO₄ (2.0)	120	24	78

表1. 反应条件的优化a

Table 1. Optimization of the reaction conditions

表2. 不同脂肪族一元羧酸与6-肼基-9-苄基嘌呤的反应a

Table 2. Reaction of various aliphatic monocarboxylic acid with 6-hydrazinyl-9-benzylpurine

表3. 不同6-肼基-N9-取代嘌呤和乙酸的反应a

Table 3. Reaction of various 6-hydrazinyl-N9-substituted purine with acetic acid

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一步法合成1,2,4-三氮唑[3,4-i]嘌呤类化合物

One-Step Synthesis of 1,2,4-Triazolo[3,4-i]purine Derivatives

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