Patents by Inventor Xuenong Xu

Xuenong Xu has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 10407403
    Abstract: The present invention discloses a preparation method of cobimetinib (XL518, GDC-0973) (I). The preparation steps include: taking (2S)-2-piperidinecarboxylic acid as the raw material, performing acyl cyanation, hydrolysis, esterification and Boc protection to obtain an intermediate [2-oxo-2-((2S)-1-tert-butoxycarbonylpiperidin-2-yl)]acetate, performing an addition reaction, a reduction reaction and a cyclization reaction on the intermediate to obtain an intermediate (2S)-1-tert-butoxycarbonyl-2-(3-hydroxyazetidin-3-yl)piperidine, and performing a condensation reaction with a side chain to obtain the cobimetinib (I). The preparation method has the advantages of accessible raw materials, simple technique, high economy and environment friendliness, and is suitable for industrial production.
    Type: Grant
    Filed: May 31, 2018
    Date of Patent: September 10, 2019
    Assignee: Suzhou Miracpharma Technology Co., Ltd.
    Inventor: Xuenong Xu
  • Patent number: 10392351
    Abstract: Disclosed in the present invention is a method for preparing nilotinib intermediate 3-(4-methyl-1H-imidazol-1-yl)-5trifluoromethyl phenylamine (I). The method comprises the following steps: taking trifluorotoluene as an initial material, and preparing the nilotinib intermediate (I) by nitration, bromization, condensation and reduction successively Compared with the prior art, the preparation method has the following advantages: a relatively high yield, the raw materials are easily obtained, a concise process and few side reactions, and is adapted to industrial production, so the development of an economic technology of the bulk drug is promoted.
    Type: Grant
    Filed: July 7, 2016
    Date of Patent: August 27, 2019
    Assignees: SUZHOU LIXIN PHARMACEUTICAL CO., LTD.
    Inventors: Xuenong Xu, Deli Zeng, Liang Shu, Qing Zhang, Zhijian Bao, Jia Xue, Jian Su, Zhe Wang, Wenjie Zhou, Lingling Xie
  • Patent number: 10221155
    Abstract: A method for preparing Alectinib (Alectinib, I), comprising the preparation steps: subjecting 6-cyano-1H-indole-3-carboxylate and 4-ethyl-3-(4-morpholine-4-yl-piperidine-1-yl)-?,?-dimethylbenzyl alcohol to condensation, hydrolyzing and cyclization reaction so as to prepare Alectinib (I). The preparation method has easily available raw materials and a simple process, and is economical and environmentally friendly and suitable for industrial production.
    Type: Grant
    Filed: September 16, 2015
    Date of Patent: March 5, 2019
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY, CO., LTD.
    Inventor: Xuenong Xu
  • Patent number: 10167275
    Abstract: Disclosed are an intermediate, N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-formamidine]phenyl-2-propenamide (II), applicable in preparing AZD9291 (I) and a preparation method for the intermediate. Preparation steps of the preparation method comprise: 2-fluoro-4-methoxyaniline, serving as a starting material, undergoes amidation, substitution, nitrification, reduction and guanidination reactions to prepare N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-formamidine]phenyl-2-propenamide (II). Also disclosed is a method for preparing AZD9291 (I) by means of a cyclization reaction between the compound of a formula II and (2E)-3-dimethylamino-1-(1-methyl-1H-indol-3-yl)-2-propen-1-one (III). The preparation method has readily available raw materials and a simple process and is economical, environmentally friendly, and suitable for industrialized production.
    Type: Grant
    Filed: November 24, 2017
    Date of Patent: January 1, 2019
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Patent number: 10138224
    Abstract: Disclosed is a method for preparing Rociletinib. 2-[[4-(4-acetyl-1-piperazinyl)-2-methoxyphenyl]amino]-5 -(trifluoromethyl)-pyrimidin-4-one is obtained by means of a condensation reaction of easily obtainable raw materials 5-(trifluoromethyl)uracil and 4-(4-acetylpiperazin-1-yl)-2-methoxyaniline, an intermediate is subjected to a halogenation reaction and an amination reaction to produce Rociletinib (I). The preparation method has easily obtainable raw materials, a simple process, is economic and environmentally friendly, and is suitable for industrial production.
    Type: Grant
    Filed: April 12, 2018
    Date of Patent: November 27, 2018
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Publication number: 20180273506
    Abstract: The present invention discloses a preparation method of cobimetinib (XL518, GDC-0973) (I). The preparation steps include: taking (2S)-2-piperidinecarboxylic acid as the raw material, performing acyl cyanation, hydrolysis, esterification and Boc protection to obtain an intermediate [2-oxo-2-((2S)-1-tert-butoxycarbonylpiperidin-2-yl)]acetate, performing an addition reaction, a reduction reaction and a cyclization reaction on the intermediate to obtain an intermediate (2S)-1-tert-butoxycarbonyl-2-(3-hydroxyazetidin-3-yl)piperidine, and performing a condensation reaction with a side chain to obtain the cobimetinib (I). The preparation method has the advantages of accessible raw materials, simple technique, high economy and environment friendliness, and is suitable for industrial production.
    Type: Application
    Filed: May 31, 2018
    Publication date: September 27, 2018
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong XU
  • Publication number: 20180230133
    Abstract: Disclosed is a method for preparing Rociletinib. 2-[[4-(4-acetyl-1-piperazinyl)-2-methoxyphenyl]amino]-5 -(trifluoromethyl)-pyrimidin-4-one is obtained by means of a condensation reaction of easily obtainable raw materials 5-(trifluoromethyl)uracil and 4-(4-acetylpiperazin-1-yl)-2-methoxyaniline, an intermediate is subjected to a halogenation reaction and an amination reaction to produce Rociletinib (I). The preparation method has easily obtainable raw materials, a simple process, is economic and environmentally friendly, and is suitable for industrial production.
    Type: Application
    Filed: April 12, 2018
    Publication date: August 16, 2018
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong XU
  • Patent number: 10039775
    Abstract: Disclosed is a preparation method for an antitumor drug AP26113 (I). The method comprises the following preparation steps: cyclizing N-[2-methoxyl-4[4-(dimethyl amino)piperid-1-yl]aniline]guanidine and N,N-dimethylamino acrylate, condensing N-[2-methoxyl-4[4-(dimethyl amino)piperid-1-yl]aniline]guanidine and 4-(dimethyl phosphitylate)aniline, and chlorinating N-[2-methoxyl-4[4-(dimethyl amino)piperid-1-yl]aniline]guanidine and a chlorinating agent, sequentially, so as to prepare AP26113 (I). The preparation method adopts easily-obtained raw materials, causes few side reactions, and is economical, environmentally friendly, and suitable for industrial production.
    Type: Grant
    Filed: November 24, 2017
    Date of Patent: August 7, 2018
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Patent number: 10005726
    Abstract: Disclosed are an intermediate N-cyclopentyl-2-methoxy-5-(N,N-dimethyl-formamido)-3-pyrrylformonitrile (II) for preparing ribociclib and a preparation method therefor. The preparation method comprises the following preparation steps: carrying out halogenating reaction on N,N-dimethyl-2-carbonyl-propanamide (IV) to obtain N,N-dimethyl-1-halo-2-carbonyl-propanamide (V); carrying out substitution reaction on the intermediate (V) and malononitrile to prepare N,N-dimethyl-1,1-dicyano-3-carbonyl-butyramide (VI); carrying out cyclization reaction on the intermediate (VI) to prepare 2-methoxy-5-(N,N-dimethyl-formamido)-3-pyrrylformonitrile (VII); and carrying out coupling reaction on the intermediate (VII) and bromocyclopentane to obtain the intermediate N-cyclopentyl-2-methoxy-5-(N,N-dimethyl-formanido)-3-pyrrylformonitrile (II) for preparing ribociclib. The intermediate (II) and N-[5-(1-piperazino)-2-piperidyl]guanidine (III) are subjected to condensation reaction to prepare ribociclib.
    Type: Grant
    Filed: November 22, 2017
    Date of Patent: June 26, 2018
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Patent number: 10005778
    Abstract: This invention reveals the method for preparing Palbociclib (I). The preparation includes: produce the 6-acetyl-5-methyl-2-substituent-pyrido[2,3-d]pyrimidin-7(8H)-one (IV) through the ring-closure reaction by using accessible raw materials of 1-(4-amino-2-substituent-5-pyrimidinyl) ethanone (II) and acetylacetic ester (III); produce the 6-acetyl-8-cyclopentyl-5-methyl-2-substituent-pyrido[2,3-d]pyrimidin-7(8H)-one (VI) through the substitution reaction between the intermediate (IV) and the cyclopentane halide (V); prepare the Palbociclib (I) through the condensation and hydrolysis reactions between the intermediate (VI) and 4-(6-amino-3-pyridinyl)-1-piperazinecarboxylic acid 1,1-dimethylethyl ester (VII). This method for preparing Palbociclib (I) is characterized by easily available raw materials, concise process and economy and environmental protection, and it is suitable for industrialized production.
    Type: Grant
    Filed: May 16, 2017
    Date of Patent: June 26, 2018
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Patent number: 9969718
    Abstract: Disclosed is an intermediate of bemaciclib (also referred to as abemaciclib) having a structure of Formula II, and preparation methods therefor. The preparation methods may comprise condensation, amidine reaction, cyclization and/or other unit reactions. Bemaciclib is obtained through a guanidination reaction and a cyclization reaction using the bemaciclib intermediate disclosed herein as a starting material. starting materials for the preparation methods disclosed herein are easily available, the procedures are simple, and the preparation methods are economical, environmentally friendly and suitable for industrial production.
    Type: Grant
    Filed: July 7, 2017
    Date of Patent: May 15, 2018
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Publication number: 20180093950
    Abstract: Disclosed are an intermediate N-cyclopentyl-2-methoxy-5-(N,N-dimethyl-formamido)-3-pyrrylformonitrile (II) for preparing ribociclib and a preparation method therefor. The preparation method comprises the following preparation steps: carrying out halogenating reaction on N,N-dimethyl-2-carbonyl-propanamide (IV) to obtain N,N-dimethyl-1-halo-2-carbonyl-propanamide (V); carrying out substitution reaction on the intermediate (V) and malononitrile to prepare N,N-dimethyl-1,1-dicyano-3-carbonyl-butyramide (VI); carrying out cyclization reaction on the intermediate (VI) to prepare 2-methoxy-5-(N,N-dimethyl-formamido)-3-pyrrylformonitrile (VII); and carrying out coupling reaction on the intermediate (VII) and bromocyclopentane to obtain the intermediate N-cyclopentyl-2-methoxy-5-(N,N-dimethyl-formanido)-3-pyrrylformonitrile (II) for preparing ribociclib. The intermediate (II) and N-[5-(1-piperazino)-2-piperidyl]guanidine (III) are subjected to condensation reaction to prepare ribociclib.
    Type: Application
    Filed: November 22, 2017
    Publication date: April 5, 2018
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong XU
  • Publication number: 20180072706
    Abstract: Disclosed are an intermediate, N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-formamidine]phenyl-2-propenamide (II), applicable in preparing AZD9291 (I) and a preparation method for the intermediate. Preparation steps of the preparation method comprise: 2-fluoro-4-methoxyaniline, serving as a starting material, undergoes amidation, substitution, nitrification, reduction and guanidination reactions to prepare N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-formamidine]phenyl-2-propenamide (II). Also disclosed is a method for preparing AZD9291 (I) by means of a cyclization reaction between the compound of a formula II and (2E)-3-dimethylamino-1-(1-methyl-1H-indol-3-yl)-2-propen-1-one (III). The preparation method has readily available raw materials and a simple process and is economical, environmentally friendly, and suitable for industrialized production.
    Type: Application
    Filed: November 24, 2017
    Publication date: March 15, 2018
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong XU
  • Publication number: 20180071324
    Abstract: Disclosed is a preparation method for an antitumor drug AP26113 (I). The method comprises the following preparation steps: cyclizing N-[2-methoxyl-4[4-(dimethyl amino)piperid-1-yl]aniline]guanidine and N,N-dimethylamino acrylate, condensing N-[2-methoxyl-4[4-(dimethyl amino)piperid-1-yl]aniline]guanidine and 4-(dimethyl phosphitylate)aniline, and chlorinating N-[2-methoxyl-4[4-(dimethyl amino)piperid-1-yl]aniline]guanidine and a chlorinating agent, sequentially, so as to prepare AP26113 (I). The preparation method adopts easily-obtained raw materials, causes few side reactions, and is economical, environmentally friendly, and suitable for industrial production.
    Type: Application
    Filed: November 24, 2017
    Publication date: March 15, 2018
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong XU
  • Patent number: 9856215
    Abstract: Disclosed is a preparation method of nintedanib (I), comprising the following steps: carrying out a condensation reaction on 4-(R acetate-2-yl)-3-nitrobenzoate (II) and trimethyl orthobenzoate to obtain (E)-4-[(2-methoxybenzylidene) R acetate-2-yl]-3-nitrobenzoate (III); carrying out a substitution reaction on the compound (EI) and N-(4-aminophenyl)-N-methyl-2-(4-methyl piperazine-1-yl) acetamide (IV) under the action of an acid-binding agent to generate (Z)-4-{[2-(N-methyl-2-(4-methyl piperazine-1-yl) acetamido-aniline) benzylidene] R acetate-2-yl}-3-nitrobenzoate (V); and sequentially carrying out reduction reactions and cyc-lization reactions on the compound (V) to prepare the nintedanib (I). The preparation method has an easily obtained raw material and a simple process, is economical and environmentally friendly, and is suitable for industrial production.
    Type: Grant
    Filed: March 8, 2017
    Date of Patent: January 2, 2018
    Assignee: SUZHOU MIRAPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Patent number: 9850244
    Abstract: The invention discloses a method for preparing Palbociclib (I). The preparation method comprises the steps of: causing a ring-closing reaction of 2-acetyl-2-butenoic acid methyl ester and malononitrile to occur in an alkaline condition to generate 1,4,5,6-tetrahydro-2-methoxyl-4-methyl-5-acetyl-6-oxy-3-pyridine carbonitrile (II); causing a substitution reaction of the intermediate(II) and halogenated cyclopentane(III) to occur under the effect of acid binding agent to generate N-cyclopentyl-1,4,5,6-tetrahydro-2-methoxyl-4-methyl-5-acetyl-6-oxy-3-pyridinecarbonitrile (IV); causing a condensation reaction of the intermediate(IV) and N-[5-(1-piperazinyl)-2-pyridinyl]guanidine (V) to occur to generate 6-acetyl-8-cyclopentyl-5,8-dihydro-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-pyrido[2,3-d]pyrimidin-7(6H)-one (VI); and causing a dehydrogenation reaction of the intermediate(VI) and sodium selenate to occur to prepare Palbociclib(I).
    Type: Grant
    Filed: May 15, 2017
    Date of Patent: December 26, 2017
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Patent number: 9845315
    Abstract: Revealed in the present invention is a method for preparing Afatinib (I): using 2-nitrile-4-[4-(N,N-dimethylamino-1-oxo-2-buten-l-yl]amino-5-[(S)-(tetrahydrofuran-3-yl)oxy]aniline (II) and 4-fluoro-3-chloroaniline (III) as starting materials, and respectively performing a condensation and cyclization reaction with N,N-dimethylformamide dimethylacetal (IV) to prepare Afatinib (I), wherein the method significantly reduces the manufacturing steps of Afatinib and greatly lower the costs. In addition, also provided in the present invention is a method for preparing an intermediate of Afatinib, wherein the method has a stable process, uses readily available starting materials, has a low cost, and all the reactions are classic reactions, suitable for meeting amplification requirements in the industry.
    Type: Grant
    Filed: December 3, 2015
    Date of Patent: December 19, 2017
    Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Publication number: 20170305884
    Abstract: Disclosed are an intermediate of bemaciclib or abemaciclib and a preparation method therefor. The preparation method comprises condensation, amidine reaction, cyclization and other unit reactions. Serving the intermediate of bemaciclib as a raw material, bemaciclib is obtained through the guanidination reaction and the cyclization reaction. According to the preparation method, the raw material is easily available, the procedure is simple, and the preparation method is economical, environmentally friendly and suitable for industrial production.
    Type: Application
    Filed: July 7, 2017
    Publication date: October 26, 2017
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong Xu
  • Publication number: 20170247380
    Abstract: This invention reveals the method for preparing Palbociclib (I). The preparation includes: produce the 6-acetyl-5-methyl-2-substituent-pyrido[2,3-d]pyrimidin-7(8H)-one (IV) through the ring-closure reaction by using accessible raw materials of 1-(4-amino-2-substituent-5-pyrimidinyl) ethanone (II) and acetylacetic ester (III); produce the 6-acetyl-8-cyclopentyl-5-methyl-2-substituent-pyrido[2,3-d]pyrimidin-7(8H)-one (VI) through the substitution reaction between the intermediate (IV) and the cyclopentane halide (V); prepare the Palbociclib (I) through the condensation and hydrolysis reactions between the intermediate (VI) and 4-(6-amino-3-pyridinyl)-1-piperazinecarboxylic acid 1,1-dimethylethyl ester (VII). This method for preparing Palbociclib (I) is characterized by easily available raw materials, concise process and economy and environmental protection, and it is suitable for industrialized production.
    Type: Application
    Filed: May 16, 2017
    Publication date: August 31, 2017
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong XU
  • Publication number: 20170247379
    Abstract: The invention discloses a method for preparing Palbociclib (I). The preparation method comprises the steps of: causing a ring-closing reaction of 2-acetyl-2-butenoic acid methyl ester and malononitrile to occur in an alkaline condition to generate 1,4,5,6-tetrahydro-2-methoxyl-4-methyl-5-acetyl-6-oxy-3-pyridine carbonitrile (II); causing a substitution reaction of the intermediate(II) and halogenated cyclopentane(III) to occur under the effect of acid binding agent to generate N-cyclopentyl-1,4,5,6-tetrahydro-2-methoxyl-4-methyl-5-acetyl-6-oxy-3-pyridinecarbonitrile (IV); causing a condensation reaction of the intermediate(IV) and N-[5-(1-piperazinyl)-2-pyridinyl]guanidine (V) to occur to generate 6-acetyl-8-cyclopentyl-5,8-dihydro-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]-pyrido[2,3-d]pyrimidin-7(6H)-one (VI); and causing a dehydrogenation reaction of the intermediate(VI) and sodium selenate to occur to prepare Palbociclib(I).
    Type: Application
    Filed: May 15, 2017
    Publication date: August 31, 2017
    Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
    Inventor: Xuenong XU