Synthesis of ATP-competitive inhibitor Wye-125132
10.7644/j.issn.1674-9960.2016.08.006
- VernacularTitle:ATP-竞争性mTOR抑制剂Wye-125132的合成
- Author:
Xiang LUO
;
Shuang CAO
;
Yihong YANG
;
Wu ZHONG
- Publication Type:Journal Article
- Keywords:
mTOR inhibitor;
Wye-125132;
ATP-competitive inhibitor
- From:
Military Medical Sciences
2016;40(8):643-645,685
- CountryChina
- Language:Chinese
-
Abstract:
Objective To synthesize Wye-125132,an inhibitor of mTOR,and to establish a synthetic route for industrial production.Methods Barbituric acid was used as the raw material to synthesize the intermediate 2, 4, 6-trichrolo-pyrimidine-5-carbaldehyde 2 via Vilsmeier-Haack and chlorination reaction, while intermediate 5 was prepared via 3-step reaction from 1,4-dioxaspiro-[4,5]decan-8-one.The condensation of 2 and 5 was followed by substitution reaction to obtain the key intermediate 7.The side chain 9 was prepared by 3-step reaction from bromine aniline.Then the title product 1 was obtained with the reaction of Suzuki cross-coupling of 7 and 9.The structures of intermediate and target compounds were confirmed by MS and 1 H-NMR.Results and Conclusion Compared with the method reported in the literature,this new synthesis method possesses some advantages, such as ready availablity of raw materials, simple operation, mild reaction conditions and easy disposal of products.The total yield is 13.2%,and the purity of the target compound is 99.77%.
