Patents Assigned to SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.
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Patent number: 10407403Abstract: 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: GrantFiled: May 31, 2018Date of Patent: September 10, 2019Assignee: Suzhou Miracpharma Technology Co., Ltd.Inventor: Xuenong Xu
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Patent number: 10221155Abstract: 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: GrantFiled: September 16, 2015Date of Patent: March 5, 2019Assignee: SUZHOU MIRACPHARMA TECHNOLOGY, CO., LTD.Inventor: Xuenong Xu
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Patent number: 10167275Abstract: 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: GrantFiled: November 24, 2017Date of Patent: January 1, 2019Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Patent number: 10138224Abstract: 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: GrantFiled: April 12, 2018Date of Patent: November 27, 2018Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Publication number: 20180273506Abstract: 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: ApplicationFiled: May 31, 2018Publication date: September 27, 2018Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU
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Publication number: 20180230133Abstract: 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: ApplicationFiled: April 12, 2018Publication date: August 16, 2018Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU
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Patent number: 10039775Abstract: 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: GrantFiled: November 24, 2017Date of Patent: August 7, 2018Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Patent number: 10005726Abstract: 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: GrantFiled: November 22, 2017Date of Patent: June 26, 2018Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Patent number: 10005778Abstract: 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: GrantFiled: May 16, 2017Date of Patent: June 26, 2018Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Patent number: 9969718Abstract: 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: GrantFiled: July 7, 2017Date of Patent: May 15, 2018Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Publication number: 20180093950Abstract: 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: ApplicationFiled: November 22, 2017Publication date: April 5, 2018Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU
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Publication number: 20180071324Abstract: 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: ApplicationFiled: November 24, 2017Publication date: March 15, 2018Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU
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Publication number: 20180072706Abstract: 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: ApplicationFiled: November 24, 2017Publication date: March 15, 2018Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU
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Patent number: 9850244Abstract: 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: GrantFiled: May 15, 2017Date of Patent: December 26, 2017Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Patent number: 9845315Abstract: 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: GrantFiled: December 3, 2015Date of Patent: December 19, 2017Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Publication number: 20170305884Abstract: 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: ApplicationFiled: July 7, 2017Publication date: October 26, 2017Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Publication number: 20170247380Abstract: 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: ApplicationFiled: May 16, 2017Publication date: August 31, 2017Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU
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Publication number: 20170247379Abstract: 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: ApplicationFiled: May 15, 2017Publication date: August 31, 2017Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU
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Patent number: 9688685Abstract: Disclosed is a method for preparing Volasertib (I), comprising the following steps: an intermediate 2-amino-7-ethyl-7,8-dihydro-5-methyl-8-isopropyl-(7R)-6(5H)-pteridinone (II) is nucleophilically substituted with an intermediate N-[trans-4-[4-(cylopropylmethyl)-1-piperazinyl]cyclohexyl]-4-halo-3-methoxylbenzamide (III), so as to prepare Volasertib (I). The preparation method has a simple process, mild conditions and few side effects, which meets the requirements for industrial enlargement. In addition, also disclosed are an intermediate 2-amino-7-ethyl-7,8-dihydro-5-methyl-8-isopropyl-(7R)-6(5H)-pteridinone (II) and an intermediate N-[trans-4-[4-(cylopropylmethyl)-1-piperazinyl]cyclohexyl]-4-halo-3-methoxylbenza-mide (III) of Volasertib and the preparation methods thereof.Type: GrantFiled: November 25, 2016Date of Patent: June 27, 2017Assignee: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong Xu
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Publication number: 20170174625Abstract: 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: ApplicationFiled: March 8, 2017Publication date: June 22, 2017Applicant: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.Inventor: Xuenong XU