Patents Assigned to Zhejiang Huahai Pharmaceutical Co., Ltd.
  • Publication number: 20200087256
    Abstract: Disclosed is a new method for preparing a donepezil pamoate (1-benzyl-4-[(5,6-dimethoxyindan-2-one)methyl]piperidine pamoate). The donepezil pamoate prepared by using the method has a high purity and a good flowability.
    Type: Application
    Filed: June 5, 2018
    Publication date: March 19, 2020
    Applicants: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD., SHANGHAI AOBO PHARMTECH, INC., LTD.
    Inventors: Wei XU, Xi CHEN, Hong GU
  • Publication number: 20200087273
    Abstract: The present invention relates to a new preparation method for escitalopram pamoate ((S)-(+)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-cyanoisob enzofuran pamoate), wherein the method is environmentally friendly and pollution-free, and the escitalopram pamoate prepared by means of the method has a high purity and a good repeatability.
    Type: Application
    Filed: June 5, 2018
    Publication date: March 19, 2020
    Applicants: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD., SHANGHAI AOBO PHARMTECH, INC., LTD.
    Inventors: Wei XU, Xi CHEN, Hong GU
  • Patent number: 10590154
    Abstract: 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.
    Type: Grant
    Filed: November 2, 2016
    Date of Patent: March 17, 2020
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD, SHANGHAI AOBO PHARMTECH, INC., LTD.
    Inventors: Siyuan Li, Shaoxiao Gui, Genliang Wang, Jicheng Zhang, Luning Huang, Anping Tao, Hong Gu
  • Patent number: 10577309
    Abstract: Provided is a method for preparing a pregabalin intermediate 3-isobutylglutaric acid monoamide. The method comprises: 1) adding 3-isobutylglutaric acid and urea into a first organic solvent; 2) keeping warm and refluxing when heated to 100-140° C.; 3) adding water when cooled to 70-90° C.; 4) adding an ion membrane alkaline when cooled to 40-60° C., adjusting the pH to 11.0-14.0, then keeping warm at 40-60° C.; 5) when finished keeping warm, removing an organic layer; 6) adding an acid into the water layer to adjust the pH to 1.0-3.0; 7) extracting the solution acquired in step 6) by using a second organic solvent of a total volume of V, vacuum distilling 0.5-0.6 V of the organic solvent from an organic layer acquired by extraction; and 8) cooling to 0-15° C. and crystallizing to acquire 3-isobutylglutaric acid monoamide.
    Type: Grant
    Filed: June 21, 2017
    Date of Patent: March 3, 2020
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICALS CO., LTD, ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL CO., LTD
    Inventors: Pan Guo, Musong Liu, Zengle Zhou, Wenling Zhang, Peng Wang
  • Patent number: 10550109
    Abstract: Disclosed are a crystal form of brexpiprazole and a preparation method therefor. The X-ray powder diffraction pattern, which is detected with Cu—K? radiation, of the crystal form of brexpiprazole has characteristic peaks at the positions where 2? is about 9.1±0.2, 15.2±0.2, 15.7±0.2, 17.6±0.2, 18.1±0.2, 24.4±0.2. The crystal form I of brexpiprazole has a high purity, good stability and good reproducibility, and is suitable for industrial production.
    Type: Grant
    Filed: May 12, 2017
    Date of Patent: February 4, 2020
    Assignees: Zhejiang Huahai Pharmaceutical Co., Ltd, Shanghai Aobo Pharmtech, Inc., Ltd.
    Inventors: Yinglu Jiao, Handa Li, Boyu Wang, Luning Huang, Xi Chen, Hong Gu
  • Patent number: 10538507
    Abstract: Provided is a purifying method for dabigatran etexilate free base, comprising subjecting a dabigatran etexilate free base crude product to water slurrying to obtain a crude product B; then conducting recrystallization on the crude product B with acetone and water to obtain a crude product C; and subsequently, purifying the crude product C with a mixed solvent of tetrahydrofuran and ethyl acetate, filtering and drying to obtain a dabigatran etexilate free base finished product. The purifying method of the present invention can effectively remove various impurities and is suitable for workshop production. Salts and water-soluble organic impurities are removed by purified water slurrying, impurities with a high polarity are removed by purifying with an acetone-water solution, and impurities with a low polarity are removed by purifying with a mixed solvent of tetrahydrofuran and ethyl acetate.
    Type: Grant
    Filed: May 24, 2017
    Date of Patent: January 21, 2020
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD, ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL CO., LTD.
    Inventors: Lingjie Chen, Wenling Zhang, Peng Wang
  • Patent number: 10508076
    Abstract: Provided is a method for resolution of formula 4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxy-methyl benzonitrile as an enantiomer thereof, comprising the following steps: a salt of (S)-4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxymethyl benzonitrile with a resolving agent D-(+)di-p-toluoyl tartaric acid was crystallized in a resolving solvent; the method is characterized in that the resolving solvent is an ether solvent. Also provided is a new crystal form of the resolved intermediate.
    Type: Grant
    Filed: February 22, 2019
    Date of Patent: December 17, 2019
    Assignee: Zhejiang huahai Pharmaceuticals Co., Ltd.
    Inventors: Zunjun Liang, Siqi Hu, Caihua Peng, Wenfeng Huang, Qifeng Lu, Guoliang Tu
  • Patent number: 10456405
    Abstract: Provided are a compound of the formula below, and a pharmaceutically acceptable salt or stereoisomer thereof that can be used for treating cardiovascular diseases and compositions containing the compounds. The compounds, a pharmaceutically acceptable salt or stereoisomer thereof and the compositions can improve lipid metabolism disorders by increasing high-density lipoprotein cholesterol in blood; in addition, the compounds, a pharmaceutically acceptable salt or stereoisomer thereof and the compositions can also release nitric oxide, and reduce the onset risk of cardiovascular diseases by means of relaxing blood vessels, lowering blood pressure, inhibiting platelet adhesion and aggregation and maintaining vascular tension, and thus play an important role in preventing and treating the occurrence and development of cardiovascular diseases.
    Type: Grant
    Filed: September 6, 2016
    Date of Patent: October 29, 2019
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD, SHANGHAI SYNERGY PHARMACEUTICAL SCIENCES CO., LTD
    Inventors: Jian Ge, Yunfei Li, Zhen Zhang, Yijin Wang, Jiamiao Wang, Tao Cheng
  • Patent number: 10385079
    Abstract: 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, C1-C6 alkyl, and C1-C6 alkoxy, and R1 is C1-C6 alkyl or C1-C6 alkyl 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, C1-C6 alkyl, and C1-C6 alkoxy.
    Type: Grant
    Filed: November 2, 2016
    Date of Patent: August 20, 2019
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD, SHANGHAI SYNCORES TECHNOLOGIES INC. LTD.
    Inventors: Siyuan Li, Shaoxiao Gui, Jicheng Zhang, Luning Huang, Anping Tao, Hong Gu
  • Patent number: 10329290
    Abstract: 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° 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.
    Type: Grant
    Filed: November 2, 2016
    Date of Patent: June 25, 2019
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD, SHANGHAI SYNCORES TECHNOLOGIES INC. LTD.
    Inventors: Haisheng Fan, Xiaowen Guo, Luning Huang, Hong Gu
  • Publication number: 20190152894
    Abstract: Provided is a method for preparing a pregabalin intermediate 3-isobutylglutaric acid monoamide. The method comprises: 1) adding 3-isobutylglutaric acid and urea into a first organic solvent; 2) keeping warm and refluxing when heated to 100-140° C.; 3) adding water when cooled to 70-90° C.; 4) adding an ion membrane alkaline when cooled to 40-60° C., adjusting the pH to 11.0-14.0, then keeping warm at 40-60° C.; 5) when finished keeping warm, removing an organic layer; 6) adding an acid into the water layer to adjust the pH to 1.0-3.0; 7) extracting the solution acquired in step 6) by using a second organic solvent of a total volume of V, vacuum distilling 0.5-0.6 V of the organic solvent from an organic layer acquired by extraction; and 8) cooling to 0-15° C. and crystallizing to acquire 3-isobutylglutaric acid monoamide.
    Type: Application
    Filed: June 21, 2017
    Publication date: May 23, 2019
    Applicants: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD, ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL CO., LTD
    Inventors: Pan GUO, Musong LIU, Zengle ZHOU, Wenling ZHANG, Peng WANG
  • Patent number: 10227293
    Abstract: The present invention relates to a method for preparing a citalopram diol represented by formula IV, comprising the following steps: in the existence of an auxiliary reagent of metal salt, allowing 5-cyanophthalide to sequentially subjected to Grignard addition reactions with p-fluorophenyl magnesium halide and N, N-dimethylaminopropyl magnesium halide in an organic solvent; and after the reactions are completed, performing hydrolysis and separation to obtain citalopram diol represented by formula IV. In the present invention, by adding an auxiliary reagent of metal salt, the activity and the selectivity of the Grignard reactions are remarkably improved, and the reaction yield is obviously enhanced.
    Type: Grant
    Filed: June 9, 2015
    Date of Patent: March 12, 2019
    Assignees: Zhejiang Huahai Pharmaceutical Co., Ltd, Zhejiang Huahai Licheng Pharmaceutical Co., Ltd, Zhejiang Huahai Jiancheng Pharmaceutical Co., Ltd
    Inventors: Zunjun Liang, Weifeng Xiao, Caihua Peng, Wenfeng Huang, Guoliang Tu
  • Patent number: 10189760
    Abstract: 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: R1 and R2 are each independently selected from hydrogen, C1-C12 linear or branched alkyl, C3-C12 cycloalkyl, C2-C12 alkenyl, C2-C12 alkynyl and C7-C12 arylalkyl. 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.
    Type: Grant
    Filed: October 9, 2015
    Date of Patent: January 29, 2019
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD., SHANGHAI SYNCORES TECHNOLOGIES INC. LTD.
    Inventors: Jian Hong, Yusheng Wang, Boyu Wang, Luning Huang, Eric Gu
  • Patent number: 10173965
    Abstract: The present invention provides a method for preparing a pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid without solvent. The method comprises the following steps: a) cooling an ammonia water system to a certain temperature; b) adding 3-isobutylglutaric anhydride dropwise to the system, then keeping temperature, and reacting; c) after completing the reaction, adding an acid to the system to adjust pH; d) after adjusting pH, cooling, then keeping temperature, crystallizing, then suction filtering and drying; and e) adding a solvent to the dried substance, slurrying, and suction filtering and drying to obtain the final product. The method provided in the present invention for preparing 3-carbamoymethyl-5-methylhexanoic acid is high-yield, green, environmentally-friendly, simple and convenient, and of less pollution.
    Type: Grant
    Filed: March 25, 2016
    Date of Patent: January 8, 2019
    Assignee: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.
    Inventors: Musong Liu, Wenling Zhang, Peng Wang
  • Patent number: 10131625
    Abstract: The present invention provides a method for recycling 3-carbamoylmethyl-5-methylhexanoic acid from 3-carba carbamoylmethyl moymethyl-5-methylhexanoic acid chiral resolving mother liquor. The method comprises the following steps: (a) distilling 3-carbamoylmethyl-5-methylhexanoic acid chiral resolving mother liquor, adding aromatic hydrocarbon, heating to dissolve, keeping the temperature and stirring; (b) after completing the reaction in step (a), cooling the reaction solution to 30-60° C., then adding alkali liquor dropwise, keeping the temperature and reacting; and (c) after completing the reaction in step (b), cooling the reactant to 20-30° C., layering, adjusting the pH of the separated water layer to 1 to 2, performing extraction by using an organic solvent, distilling an organic phase under a reduced pressure, and crystallizing at 0±5° C. to obtain 3-carbamoylmethyl-5-methylhexanoic acid.
    Type: Grant
    Filed: October 13, 2015
    Date of Patent: November 20, 2018
    Assignee: Zhejiang Huahai Pharmaceutical Co., Ltd.
    Inventors: Shudong Wang, Xuehai You, Wenling Zhang
  • Publication number: 20180250305
    Abstract: Provided are a type of compounds that can be used for treating cardiovascular diseases and compositions containing the compounds. The compounds and the compositions can improve lipid metabolism disorders by increasing high-density lipoprotein cholesterol in blood; in addition, the compounds and the compositions can also release nitric oxide, and reduce the onset risk of cardiovascular diseases by means of relaxing blood vessels, lowering blood pressure, inhibiting platelet adhesion and aggregation and maintaining vascular tension, and thus play an important role in preventing and treating the occurrence and development of cardiovascular diseases.
    Type: Application
    Filed: September 6, 2016
    Publication date: September 6, 2018
    Applicants: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD., SHANGHAI SYNERGY PHARMACEUTICAL SCIENCES CO., LTD
    Inventors: Jian GE, Yunfei LI, Zhen ZHANG, Yijin WANG, Jiamiao WANG, Tao CHENG
  • Publication number: 20180155326
    Abstract: The present invention uses a candesartan cyclic compound as a starting material and performs thereon a three-step reaction of forming tetrazole, hydrolysis and adding a protecting group to directly obtain trityl candesartan without separating an intermediate product via crystallization. The operating process is simple and thus is more applicable to industrial production.
    Type: Application
    Filed: June 5, 2015
    Publication date: June 7, 2018
    Applicant: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.
    Inventors: Enmin Lin, Mengjian Mou, Guoliang Tu, Wenfeng Huang
  • Patent number: 9951036
    Abstract: 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.
    Type: Grant
    Filed: June 19, 2015
    Date of Patent: April 24, 2018
    Assignees: SHANGHAI SYNCORES TECHNOLOGIES INC. LTD., ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD
    Inventors: Wenjing Liao, Xiaowen Guo, Luning Huang, Eric Gu
  • Patent number: 9926286
    Abstract: 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.
    Type: Grant
    Filed: March 25, 2015
    Date of Patent: March 27, 2018
    Assignees: SHANGHAI SYNCORES TECHNOLOGIES INC. LTD., ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD
    Inventors: Caide Tang, Gang Wang, Boyu Wang, Luning Huang, Eric Gu
  • Patent number: 9873651
    Abstract: 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: R1 and R2 are each independently selected from hydrogen, C1-C12 linear or branched alkyl, C3-C12 cycloalkyl, C2-C12 alkenyl, C2-C12 alkynyl and C7-C12 arylalkyl. 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.
    Type: Grant
    Filed: October 9, 2015
    Date of Patent: January 23, 2018
    Assignees: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD, SHANGHAI SYNCORES TECHNOLOGIES INC. LTD.
    Inventors: Jian Hong, Yusheng Wang, Boyu Wang, Luning Huang, Eric Gu