Zhejiang Huahai Pharmaceutical Co., Ltd.

Shanghai Syncores Technologies Inc. Ltd.

Eric Gu

Luning Huang

Boyu Wang

Wenjing Liao

Gang Wang

Anping Tao

Xiaowen Guo

Jicheng Zhang

Jian Hong

Caide Tang

Jianfeng Ge

Yusheng Wang

The present application relates to a synthesis method for cariprazine, comprising performing an acylation reaction between a compound represented by formula (I) and dimethylcarbamoyl chloride in a reaction solvent in the presence of an aqueous solution of an inorganic base, so as to obtain the cariprazine compound represented by formula (II). The synthesis method overcomes defects in the prior art such as a long reaction time, large size impurities and the difficulty of purification, and provides a new method suitable for commercial production wherein the reaction is fast, impurity sizes are small, the product is easily purified, the purity of the product can reach 99.0% or more, and the yield is high. 

Synthesis method for cariprazine

Disclosed is a method for synthesizing a sitagliptin intermediate, the method comprising: in the presence of hydrogen and a transition metal catalyst having a chiral phosphine ligand, subjecting a compound of formula II to an asymmetric reductive amination with ammonia or ammonium salt in a proper organic solvent under the condition of adding an acidic additive to produce a compound of formula I, wherein, an R- or S-configuration of a stereocenter is represented by *; the compound of formula I of R configuration can be used to prepare sitagliptin, and a reaction formula is as follows: Rand Rare each independently selected from hydrogen, C-Clinear or branched alkyl, C-Ccycloalkyl, C-Calkenyl, C-Calkynyl and C-Carylalkyl. The method has a high yield and a high ee % value, a mild reaction condition and a low production cost, and is simple to operate, convenient to purify, environmental friendly and suitable for industrial production. 

Method for preparing sitagliptin intermediate via asymmetrical reduction method

Provide in the present invention is a method for preparing canagliflozin intermediate 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene. The method comprises a compound, shown as formula (II), of (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]ketone being reduced under the action of a directly used borane solution or borane locally produced by reacting alkali metal borohydride with a Lewis acid in a suitable solvent and at a suitable temperature, so as to obtain the compound of formula (I) of 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene. The preparation method avoids the use of expensive reductive agents and guarantees the complete conversion of raw materials, wherein the post-treatment is simple, the purity of product obtained is high, the reaction yield is high, in the preparation method is simple and convenient, and can easily be used in industry.

Method for preparing canagliflozin intermediate 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene

The present invention provides a new intermediate II and a method for synthesizing the same. The method comprises: (a) firstly diazotizing a compound of formula I as a raw material, and then halogenating to obtain an intermediate II; and (b) reacting the intermediate II with a compound III to obtain a compound IV, hydrolyzing the obtained compound IV directly without being separated to obtain Vortioxetine represented by compound V. The intermediate II can be used for synthesizing Vortioxetine. 

Vortioxetine intermediate and synthesis process thereof

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Shanghai, China

Eric Gu