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7182334 
Journal Article 
Efficient Synthetic Approaches to Uric Acid Transporter 1 Inhibitors Bearing Alkoxyl Group-Substituted Triazoles 
Tian He; Wu Jingwei; Liu Yuqiang; Xie Yafei; Wang Jianwu; Zhao Guilong; , 
2017 
1 
Youji Huaxue / Chinese Journal of Organic Chemistry
ISSN: 0253-2786 
SCIENCE PRESS 
BEIJING 
1748-1756 
WOS:000408601000012 
Uric acid transporter 1 (URAT1) inhibitors bearing alkoxy group-substituted triazoles 3-(4-(4-cyclopropylnaphthalen-1-y1)-5-methoxy-4H-1,2,4-triazol-3-yl)propanoic acid (1a) and 3-(4-(4-cyclopropylnaphthalen-1-y1)-5-ethoxy-4H1,2,4-triazol-3-yl)propanoic acid (1b) are structurally interesting lead compounds in drug design. The current synthetic approach to them suffers from quite low overall yields (3.3% and 3.0% for la and 1b, respectively). In order to explore the structure-activity relationship (SAR) of 1a and 1b, synthetic approach with higher overall yield is urgently needed. In the present study, two efficient synthetic approaches to la and 1b were developed (approaches A and B), with CuCl-catalyzed nucleophilic aromatic substitution (SNAr) reaction of bromotriazole with sodium alkoxides and SNAr reaction of methylsulfonyltriazole with sodium alkoxides as key steps, and the conditions for important steps were fully optimized. The two synthetic approaches are characterized by dramatically higher yields, and not only valuable to the further SAR exploration of 1a and 1b but also very helpful to the synthesis of heterocycles with alkoxyl groups.