CN102491919B - 去甲维拉帕米的合成方法 - Google Patents
去甲维拉帕米的合成方法 Download PDFInfo
- Publication number
- CN102491919B CN102491919B CN201110419598.4A CN201110419598A CN102491919B CN 102491919 B CN102491919 B CN 102491919B CN 201110419598 A CN201110419598 A CN 201110419598A CN 102491919 B CN102491919 B CN 102491919B
- Authority
- CN
- China
- Prior art keywords
- norverapamil
- verapamil
- reaction
- quaternary ammonium
- ammonium salt
- 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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- UPKQNCPKPOLASS-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl]amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCNCCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 UPKQNCPKPOLASS-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000001308 synthesis method Methods 0.000 title abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960001722 verapamil Drugs 0.000 claims abstract description 16
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 7
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000010189 synthetic method Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 230000006837 decompression Effects 0.000 description 12
- 238000001514 detection method Methods 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 2
- OIXUJRCCNNHWFI-UHFFFAOYSA-N 1,2-dioxane Chemical compound C1CCOOC1 OIXUJRCCNNHWFI-UHFFFAOYSA-N 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 208000000289 Esophageal Achalasia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010030136 Oesophageal achalasia Diseases 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 201000000621 achalasia Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical class C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Description
Claims (3)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201110419598.4A CN102491919B (zh) | 2011-12-15 | 2011-12-15 | 去甲维拉帕米的合成方法 |
Applications Claiming Priority (1)
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CN201110419598.4A CN102491919B (zh) | 2011-12-15 | 2011-12-15 | 去甲维拉帕米的合成方法 |
Publications (2)
Publication Number | Publication Date |
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CN102491919A CN102491919A (zh) | 2012-06-13 |
CN102491919B true CN102491919B (zh) | 2014-03-19 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN201110419598.4A Active CN102491919B (zh) | 2011-12-15 | 2011-12-15 | 去甲维拉帕米的合成方法 |
Country Status (1)
Country | Link |
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CN (1) | CN102491919B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101012185A (zh) * | 2007-02-16 | 2007-08-08 | 天津市中央药业有限公司 | 盐酸维拉帕米的精制方法 |
CN102143961A (zh) * | 2008-07-03 | 2011-08-03 | 纽尔亚商股份有限公司 | 具有nos抑制活性的苯并噁嗪、苯并噻嗪及相关化合物 |
-
2011
- 2011-12-15 CN CN201110419598.4A patent/CN102491919B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101012185A (zh) * | 2007-02-16 | 2007-08-08 | 天津市中央药业有限公司 | 盐酸维拉帕米的精制方法 |
CN102143961A (zh) * | 2008-07-03 | 2011-08-03 | 纽尔亚商股份有限公司 | 具有nos抑制活性的苯并噁嗪、苯并噻嗪及相关化合物 |
Non-Patent Citations (4)
Title |
---|
Efficient Use of Retention Time for the Analysis of 302 Drugs in Equine Plasma by Liquid Chromatography-MS/MS with Scheduled Multiple Reaction Monitoring and Instant Library Searching for Doping Control;Ying Liu et al.;《Anal. Chem.》;20110801;第83卷;6834–6841 * |
Ying Liu et al..Efficient Use of Retention Time for the Analysis of 302 Drugs in Equine Plasma by Liquid Chromatography-MS/MS with Scheduled Multiple Reaction Monitoring and Instant Library Searching for Doping Control.《Anal. Chem.》.2011,第83卷6834–6841. |
异博定合成工艺的研究;田澍;《工艺.试验》;20011231(第7期);31-34 * |
田澍.异博定合成工艺的研究.《工艺.试验》.2001,(第7期),31-34. |
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Publication number | Publication date |
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CN102491919A (zh) | 2012-06-13 |
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Effective date of registration: 20160105 Address after: 223100 No. 8, Dong Yi Road, Hongze County Industrial Park, Jiangsu, Huaian Patentee after: JIANGSU ZENJI PHARMACEUTICALS LTD. Address before: 24, building 5, block B, Nanjing science and Technology Plaza, No. 210009, new exemplary Road, Jiangsu, Nanjing Patentee before: ACESYS PHARMATECH Ltd. |
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Application publication date: 20120613 Assignee: Suzhou Zhengji Pharmaceutical Co.,Ltd. Assignor: JIANGSU ZENJI PHARMACEUTICALS LTD. Contract record no.: X2024980015147 Denomination of invention: The synthesis method of norverapamil Granted publication date: 20140319 License type: Common License Record date: 20240913 Application publication date: 20120613 Assignee: Rizhao Zhengji Pharmaceutical Co.,Ltd. Assignor: JIANGSU ZENJI PHARMACEUTICALS LTD. Contract record no.: X2024980015140 Denomination of invention: The synthesis method of norverapamil Granted publication date: 20140319 License type: Common License Record date: 20240913 |