发明名称 Preparation method of fluoro-substituted deuterated diphenylurea
摘要 A fluoro-substituted deuterated diphenylurea compound, especially 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-2-(N-(methyl-d3))picolinamide, preparing method and use for treating or preventing tumor and relative diseases thereof.
申请公布号 US8759531(B2) 申请公布日期 2014.06.24
申请号 US201113635808 申请日期 2011.03.17
申请人 Suzhou Zelgen Biopharmaccceutical Co., Ltd. 发明人 Feng Weidong;Gao Xiaoyong;Dai Xiaojun
分类号 C07C273/18;C07C275/34;C07D213/81 主分类号 C07C273/18
代理机构 Roylance, Abrams, Berdo & Goodman, L.L.P. 代理人 Roylance, Abrams, Berdo & Goodman, L.L.P.
主权项 1. A method for preparing the compound of the following formula, wherein, the method includes: (a) in an inert solvent and in the presence a base, reacting compound B2 with compound V to form said compound; wherein, X is Cl, Br, I, or OSO2CF3; or, the method includes: (b) in an inert solvent, reacting compound B′ with CD3NH2 or CD3NH2.HCl to form said compound; wherein, R is H, straight-chain or branched chain C1-C8 alkyl, or aryl; or, the method includes: (c) in an inert solvent, reacting 3-fluoro-4-aminophenol with compound V to form compound B1; in an inert solvent, reacting compound B1 with compound W to form compound M; and in an inert solvent, reacting compound M with 4-chloro-3-trifluoromethylaniline to form said compound; wherein, R is hydrogen, methyl, nitro and chlorine; said inert solvent is selected from chloroform, dichloromethane, tetrahydrofuran, 1,4-dioxane, toluene, pyridine, DMF, DMSO, or the mixed solvent thereof; said base is selected from pyridine, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, N,N-diethyl isopropyl amine, N,N-dimethylamine pyridine, N-methylmorphine, or the combination thereof; or, the method includes: (d) in an inert solvent, reacting 4-chloro-3-trifluoromethylaniline with compound W to form compound B; and in an inert solvent, reacting compound B1 with compound B to form said compound; wherein, R is hydrogen, methyl, nitro and chlorine; said inert solvent is selected from chloroform, dichloromethane, tetrahydrofuran, 1,4-dioxane, toluene, pyridine, DMF, DMSO, or the mixed solvent thereof; said base is selected from pyridine, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, N,N-diethyl isopropyl amine, N,N-dimethylamine pyridine, N-methylmorphine, or the combination thereof.
地址 Jiangsu, P.R. CN