CN101973981B - 一种1-(5-异喹啉磺酰基)高哌嗪盐酸盐的精制方法 - Google Patents
一种1-(5-异喹啉磺酰基)高哌嗪盐酸盐的精制方法 Download PDFInfo
- Publication number
- CN101973981B CN101973981B CN 201010500882 CN201010500882A CN101973981B CN 101973981 B CN101973981 B CN 101973981B CN 201010500882 CN201010500882 CN 201010500882 CN 201010500882 A CN201010500882 A CN 201010500882A CN 101973981 B CN101973981 B CN 101973981B
- Authority
- CN
- China
- Prior art keywords
- solvent
- hydrochloride
- homopiperazine hydrochloride
- fasudil hydrochloride
- isoquinoline sulfonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000000034 method Methods 0.000 title claims abstract description 15
- LFVPBERIVUNMGV-UHFFFAOYSA-N fasudil hydrochloride Chemical compound Cl.C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 LFVPBERIVUNMGV-UHFFFAOYSA-N 0.000 title abstract description 41
- 238000007670 refining Methods 0.000 title abstract description 14
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000002904 solvent Substances 0.000 claims abstract description 15
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- BQFCCCIRTOLPEF-UHFFFAOYSA-N chembl1976978 Chemical compound CC1=CC=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 BQFCCCIRTOLPEF-UHFFFAOYSA-N 0.000 claims description 10
- 238000000746 purification Methods 0.000 claims description 8
- OREHUWJLRDJJGY-UHFFFAOYSA-N 1,4-diazepane;hydrochloride Chemical compound Cl.C1CNCCNC1 OREHUWJLRDJJGY-UHFFFAOYSA-N 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims 2
- 239000012467 final product Substances 0.000 claims 1
- 239000011259 mixed solution Substances 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 12
- 239000007787 solid Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract 2
- 229960002435 fasudil Drugs 0.000 description 34
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000001291 vacuum drying Methods 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 239000007791 liquid phase Substances 0.000 description 5
- 229960004756 ethanol Drugs 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000001286 intracranial vasospasm Diseases 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- DNOWPGDHLKQUPV-UHFFFAOYSA-N [NH4+].CC#N.OP(O)([O-])=O Chemical compound [NH4+].CC#N.OP(O)([O-])=O DNOWPGDHLKQUPV-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- -1 ethanol-methyl tertbutyl ketone Chemical compound 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000003590 rho kinase inhibitor Substances 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 201010500882 CN101973981B (zh) | 2010-10-09 | 2010-10-09 | 一种1-(5-异喹啉磺酰基)高哌嗪盐酸盐的精制方法 |
Applications Claiming Priority (1)
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CN 201010500882 CN101973981B (zh) | 2010-10-09 | 2010-10-09 | 一种1-(5-异喹啉磺酰基)高哌嗪盐酸盐的精制方法 |
Publications (2)
Publication Number | Publication Date |
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CN101973981A CN101973981A (zh) | 2011-02-16 |
CN101973981B true CN101973981B (zh) | 2013-01-02 |
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CN 201010500882 Expired - Fee Related CN101973981B (zh) | 2010-10-09 | 2010-10-09 | 一种1-(5-异喹啉磺酰基)高哌嗪盐酸盐的精制方法 |
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CN (1) | CN101973981B (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102060845B (zh) * | 2010-12-28 | 2013-07-03 | 天津红日药业股份有限公司 | 一种法舒地尔的晶型ⅲ及其制备方法和用途 |
CN102060844B (zh) * | 2010-12-28 | 2014-05-28 | 天津红日药业股份有限公司 | 一种法舒地尔的晶型ⅳ及其制备方法和用途 |
CN102229601B (zh) * | 2011-05-12 | 2013-07-03 | 天津市汉康医药生物技术有限公司 | 六氢-1-(5-异喹啉磺酰基)-1(h)-1,4-二氮杂卓盐酸盐无定形化合物 |
CN102924436B (zh) * | 2012-11-30 | 2014-03-19 | 南京正大天晴制药有限公司 | 一种盐酸法舒地尔的精制方法 |
CN104098547B (zh) * | 2014-07-28 | 2016-08-24 | 天津红日药业股份有限公司 | 一种盐酸法舒地尔的精制方法 |
CN107216311B (zh) * | 2016-03-21 | 2019-09-03 | 山东诚创医药技术开发有限公司 | (s)-4-[(4-氟代异喹啉-5-基)磺酰基]-3-甲基-1,4-二氮杂环庚烷盐酸盐的精制方法 |
CN115925713A (zh) * | 2022-09-27 | 2023-04-07 | 苏州百灵威超精细材料有限公司 | 二氮杂大环类化合物中间体及其制备方法和应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4678783A (en) * | 1983-11-04 | 1987-07-07 | Asahi Kasei Kogyo Kabushiki Kaisha | Substituted isoquinolinesulfonyl compounds |
CN101723934A (zh) * | 2009-11-27 | 2010-06-09 | 天津红日药业股份有限公司 | 一种盐酸法舒地尔精制方法 |
CN101812051A (zh) * | 2010-01-25 | 2010-08-25 | 海南美兰史克制药有限公司 | 一种高纯度的盐酸法舒地尔化合物 |
-
2010
- 2010-10-09 CN CN 201010500882 patent/CN101973981B/zh not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4678783A (en) * | 1983-11-04 | 1987-07-07 | Asahi Kasei Kogyo Kabushiki Kaisha | Substituted isoquinolinesulfonyl compounds |
US4678783B1 (en) * | 1983-11-04 | 1995-04-04 | Asahi Chemical Ind | Substituted isoquinolinesulfonyl compounds |
CN101723934A (zh) * | 2009-11-27 | 2010-06-09 | 天津红日药业股份有限公司 | 一种盐酸法舒地尔精制方法 |
CN101812051A (zh) * | 2010-01-25 | 2010-08-25 | 海南美兰史克制药有限公司 | 一种高纯度的盐酸法舒地尔化合物 |
Non-Patent Citations (2)
Title |
---|
12盐酸法舒地尔的合成、药理和临床研究进展;孟祥军等;《沈阳医学院学报》;20100331;第12卷(第1期);第45-50页 * |
孟祥军等.12盐酸法舒地尔的合成、药理和临床研究进展.《沈阳医学院学报》.2010,第12卷(第1期),第45-50页. |
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CN101973981A (zh) | 2011-02-16 |
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Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant after: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant after: NANJING YOKO BIOMEDICAL R & D Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant before: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant before: Nanjing uniclever Biological Medicine Research Co.,Ltd. Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant after: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant after: Nanjing uniclever Biological Medicine Research Co.,Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant before: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant before: NANJING ACEAN MEDICINE RESEARCH Co.,Ltd. |
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Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant after: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Applicant after: NANJING YOKO BIOMEDICAL R & D Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant before: NANJING XINGANG MEDICAL Co.,Ltd. Applicant before: NANJING YOKO BIOMEDICAL R & D Ltd. |
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