Zhejiang Huahai Pharmaceutical Co., Ltd.

Shanghai Syncores Technologies Inc. Ltd.

Shanghai Aobo Pharmtech, Inc., Ltd.

Zhejiang Huahai Pharmaceuticals Co., Ltd.

Luning Huang

Hong Gu

Anping Tao

Xiaowen Guo

Jicheng Zhang

Eric Gu

Boyu Wang

Jianguo An

Haisheng Fan

Zeng Li

Yang Liu

Siyuan Li

Wenjing Liao

Jeannie Zhang

Shaoxiao Gui

Kaiqiang Shi

Gang Wang

Chen Liu

Jian Cao

Chao Huang

Hao Lu

Jian Hong

Jintao Yang

Qian Chen

Xing Li

Kai Yin

Jinfeng Yao

Jianping Lin

Xiang Ji

Huaxiang Ye

Yipeng Zhan

Yikai Zhang

Jianfeng Ge

Junzheng Huang

Yafei Jiang

Chunpeng Zi

Yuanhai Gao

Fenghao Liu

Liushan Chen

Caide Tang

Yusheng Wang

Handa Li

Yinglu Jiao

Genliang Wang

Yuanbing Guo

Xiaofei Gao

Xianliang He

Xiaosong Cheng

Kang He

Yukun Liang

Hu Su

A method for preparing lurasidone hydrochloride by reacting lurasidone free alkali reacts with hydrochloric acid in a mixed solvent of an alcoholic solvent and an alkyl halide solvent.

Method for preparing lurasidone hydrochloride

The present application relates to a method (I) for preparing a brivaracetam intermediate, comprising the steps of dissolving the compound represented by B-P and 1S,2S-diphenylethylenediamine in a solvent for resolution, crystallizing, filtering, and recrystallizing to obtain the compound represented by B-Q, which is then converted to the brivaracetam intermediate represented by B-R. This method can effectively resolve the compound represented by B-P. The present application also provides a method for preparing brivaracetam using the compound represented by B-R. The method can separate the effective components only through simple steps such as extraction, washing, drying, and concentration without requiring use of chiral chromatography column to separate isomers in the preparation process, and thus the separation process is simple, greatly reducing the production cost of brivaracetam.

Method for preparing brivaracetam and intermediate thereof

The present application relates to a method for citalopram intermediate citalopram diol. The method comprises: first mixing two Grignard reagents required for a reaction; then mixing the mixed Grignard reagents with a raw material 5-cyanophthalide in a temperature-controllable micromixer to obtain a reaction solution; then subjecting the reaction solution to the reaction by means of a reactor to obtain a citalopram diol reaction solution; and then performing operations such as quenching, concentration, extraction, acidification, and crystallization to obtain a qualified product. The citalopram diol provided in the present invention has good selectivity, high yield, high safety, safety and reliability, and little sewage discharge, and is suitable for industrial production.

Method for continuously preparing citalopram diol

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

The present invention relates to a method for preparing an intermediate (Formula IV) of sodium elagolix. The intermediate is prepared by the following route. The method has advantages of simple and safe operation, high yield, less environmental pollution, good economic effect and suitability for industrial production, wherein R represents C1-C4 substituted or unsubstituted benzyl or allyl. 

Method for preparing elagolix intermediate and composition thereof

Provided are a fosaprepitant phosphate intermediate (IV) preparation method, a fosaprepitant phosphate intermediate (IV-A) and a method of (AA) for preparing fosaprepitant dimeglumine by using the intermediate (IV-A). IV: Rand Rare independently selected from C1-C7 alkyl groups or benzyl groups; IV-A: Rand Rare independently selected from C1-C7 alkyl groups, and Rand Rare not both benzyl groups.

Fosaprepitant phosphate intermediate and preparation method therefor

The present application provides a method for preparing nintedanib. The method of the present application is carried out by using 4-halo-3-nitro-benzoic acid methyl ester (compound II) and 3-oxo-3-phenylpropionate (compound III) as raw materials, and preparing nintedanib via intermediates of methyl 4-(1-alkoxy-1,3-dioxo-3-phenyl propan-2-yl)-3-nitrobenzoate (compound IV) and methyl 3-benzoyl-2-oxoindoline-6-formate (compound V). The method for preparing nintedanib (I) provided by the present application has the advantages of using easily obtained raw materials, having a simple process, being cost effective and environmentally friendly, and is suitable for industrial-scale production.

Methods for preparing Nintedanib and intermediates thereof

Disclosed is a preparation method for a Palbociclib free base crystal form A as shown in Formula I, comprising the following steps: treating a Palbociclib free base and/or a Palbociclib salt compound by using an inorganic base in a water solvent at the temperature of 35 to 100'C. to obtain a Palbociclib free base crystal form A, the water solvent being water or mixed solvent obtained by water and an organic solvent capable of being mixed and disclosed in the water. Also disclosed is a preparation method for a Palbociclib free base crystal form B, comprising the following steps: treating a Palbociclib salt compound by using an inorganic base in a water solvent at the temperature of 0 to 20&#xb0; C. to obtain a Palbociclib free crystal form B, the water solvent being water or a mixed solvent obtained by water and an organic solvent capable of being mixed and dissolved in the water. The method is safe and convenient in operation and low in pollution, and facilitates industrial production.

Preparation methods for palbociclib free base crystal form A and crystal form B

The present invention relates to a synthesis process of suvorexant, novel compounds represented by formulas II, III, IV or V, or salts thereof for preparing suvorexant, and a method for preparing the intermediates. The preparation method uses a chiral starting material to synthesize chiral compounds represented by formulas II, III, IV or V, the compounds obtained being used for synthesizing the suvorexant. The preparation method has the advantages of simple operation, low cost, mild reaction conditions, simple post-treatment, easy to purify, high yield, high ee value for the product, and easy to industrialize. In the reaction route shown, R represents benzyl, allyl or 1-phenethyl, or optionally substituted benzyl at the 2 position to 6 position, such as 4-methoxybenzyl, 4-nitrobenzyl, 2-methylbenzyl, 4-chlorobenzyl or 3-fluorobenzyl. 

Suvorexant intermediate and preparation method thereof

The invention relates to a method for preparing an oxazolidinone intermediate. Specifically, a synthesis procedure for the intermediate comprises: directly performing a 'one-pot' reaction on a compound I, compound J or compound L without performing isolation, wherein a salt of a compound K is selected from a hydrochloride, sulfate, malate, tartrate, p-toluenesulfonate, or lactate, and wherein the symbol * in a compound indicates an atom of an R-type chirality or an S-type chirality or a racemate thereof. 

Method for preparing oxazolidinone intermediate

Disclosed are a crystal form of brexpiprazole and a preparation method therefor. The X-ray powder diffraction pattern, which is detected with Cu&#x2014;K&#x3b1; radiation, of the crystal form of brexpiprazole has characteristic peaks at the positions where 2&#x3b8; is about 9.1&#xb1;0.2, 15.2&#xb1;0.2, 15.7&#xb1;0.2, 17.6&#xb1;0.2, 18.1&#xb1;0.2, 24.4&#xb1;0.2. The crystal form I of brexpiprazole has a high purity, good stability and good reproducibility, and is suitable for industrial production.

Crystal form of brexpiprazole and preparation method therefor

The present invention relates to a preparation method for a tedizolid compound in Formula I. In Formula I, R is selected from hydrogen, formula A, formula B, benzyl or benzyl substituted by a substituent, the substituent is selected from a group consisting of halogen, nitryl, C-Calkyl, and C-Calkoxy, and Ris C-Calkyl or C-Calkyl substituted by halogen. The method comprises: generating a compound having a structure as shown in Formula C and a compound having a structure as shown in Formula D by a coupled reaction under the catalysis of a metal catalyst, a substituent of R being defined as above, where X is a leaving group, the leaving group comprising chlorine, bromine, iodine, and sulfonyl oxy such as trifluoromethane sulfonic oxy, methylsulfonyl oxy and benzenesulfonyl oxy, or benzenesulfonyl oxy substituted by one or more substituents, the substituent being selected from a group consisting of halogen, C-Calkyl, and C-Calkoxy. 

Preparation method for tedizolid, tedizolid intermediate, and preparation method therefor

Disclosed is a preparation method for a Palbociclib free base crystal form A as shown in Formula I, comprising the following steps: treating a Palbociclib free base and/or a Palbociclib salt compound by using an inorganic base in a water solvent at the temperature of 35 to 100&#xb0; C. to obtain a Palbociclib free base crystal form A, the water solvent being water or mixed solvent obtained by water and an organic solvent capable of being mixed and disclosed in the water. Also disclosed is a preparation method for a Palbociclib free base crystal form B, comprising the following steps: treating a Palbociclib salt compound by using an inorganic base in a water solvent at the temperature of 0 to 20&#xb0; C. to obtain a Palbociclib free crystal form B, the water solvent being water or a mixed solvent obtained by water and an organic solvent capable of being mixed and dissolved in the water. The method is safe and convenient in operation and low in pollution, and facilitates industrial production.

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

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Shanghai, China

Luning Huang