CN1850827A - (+)-(s-)-氯吡格雷硫酸氢盐(i型)的制备方法 - Google Patents
(+)-(s-)-氯吡格雷硫酸氢盐(i型)的制备方法 Download PDFInfo
- Publication number
- CN1850827A CN1850827A CN 200610051684 CN200610051684A CN1850827A CN 1850827 A CN1850827 A CN 1850827A CN 200610051684 CN200610051684 CN 200610051684 CN 200610051684 A CN200610051684 A CN 200610051684A CN 1850827 A CN1850827 A CN 1850827A
- Authority
- CN
- China
- Prior art keywords
- type
- clopidogrel
- preparation
- add
- ethyl acetate
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 title abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 109
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 77
- 239000003513 alkali Substances 0.000 claims abstract description 39
- 238000002360 preparation method Methods 0.000 claims abstract description 37
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000013078 crystal Substances 0.000 claims abstract description 25
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims abstract description 21
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 239000001117 sulphuric acid Substances 0.000 claims abstract description 10
- 235000011149 sulphuric acid Nutrition 0.000 claims abstract description 10
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 238000001914 filtration Methods 0.000 claims abstract description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims abstract description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims abstract description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims abstract description 4
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims abstract description 4
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims description 66
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 26
- 229960003009 clopidogrel Drugs 0.000 claims description 22
- 229940043232 butyl acetate Drugs 0.000 claims description 20
- 239000000243 solution Substances 0.000 claims description 17
- 238000009413 insulation Methods 0.000 claims description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- 238000001291 vacuum drying Methods 0.000 claims description 11
- 238000010792 warming Methods 0.000 claims description 9
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 claims description 8
- 229950010560 clopidogrel hydrochloride Drugs 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 235000017550 sodium carbonate Nutrition 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 239000012065 filter cake Substances 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- XEENARPWPCQXST-DDJQTTAYSA-N C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C.C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl Chemical group C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C.C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl XEENARPWPCQXST-DDJQTTAYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008141 laxative Substances 0.000 claims description 2
- 230000002475 laxative effect Effects 0.000 claims description 2
- XIHVAFJSGWDBGA-RSAXXLAASA-N methyl (2s)-2-(2-chlorophenyl)-2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate;hydrochloride Chemical compound Cl.C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl XIHVAFJSGWDBGA-RSAXXLAASA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 abstract 4
- 229910052801 chlorine Inorganic materials 0.000 abstract 2
- 239000000460 chlorine Substances 0.000 abstract 2
- 208000007536 Thrombosis Diseases 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 238000005406 washing Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 9
- 238000001035 drying Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- 238000000605 extraction Methods 0.000 description 6
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 5
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- GKTWGGQPFAXNFI-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetic acid methyl ester Chemical compound C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl GKTWGGQPFAXNFI-UHFFFAOYSA-N 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- KVZJMCUZKLWHHF-UHFFFAOYSA-N N1=CC=CC=C1.C1=CC=CC=2SC3=CC=CC=C3SC12 Chemical compound N1=CC=CC=C1.C1=CC=CC=2SC3=CC=CC=C3SC12 KVZJMCUZKLWHHF-UHFFFAOYSA-N 0.000 description 1
- 108010035030 Platelet Membrane Glycoprotein IIb Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
分析 | (+)-(S-)-氯吡格雷硫酸氢盐 |
IR | 2987,1753,1222,1175,841cm-1 |
XRD | 9.60,8.13,5.80,4.95,4.80,4.31,3.86,3.83,3.8,3.49d(A°) |
HPLC纯度 | 99.9% |
未知单一杂质 | ≤0.1% |
旋光 | +55.16° |
手性纯度 | 100% |
DSC熔点 | 180~184℃ |
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2006100516843A CN100396687C (zh) | 2006-05-26 | 2006-05-26 | (+)-(s-)-氯吡格雷硫酸氢盐(i型)的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2006100516843A CN100396687C (zh) | 2006-05-26 | 2006-05-26 | (+)-(s-)-氯吡格雷硫酸氢盐(i型)的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1850827A true CN1850827A (zh) | 2006-10-25 |
CN100396687C CN100396687C (zh) | 2008-06-25 |
Family
ID=37132329
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2006100516843A Active CN100396687C (zh) | 2006-05-26 | 2006-05-26 | (+)-(s-)-氯吡格雷硫酸氢盐(i型)的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN100396687C (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103044444A (zh) * | 2013-01-21 | 2013-04-17 | 上海现代哈森(商丘)药业有限公司 | 一种高纯度ⅰ型(+)-(s)-硫酸氢氯吡格雷的合成方法 |
CN107118221A (zh) * | 2017-05-24 | 2017-09-01 | 常州制药厂有限公司 | 一种硫酸氢氯吡格雷晶型i制备方法 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101864006A (zh) * | 2010-07-16 | 2010-10-20 | 北京化工大学常州先进材料研究院 | 含环缩醛的硫杂蒽酮类光引发剂及其制备方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE349451T1 (de) * | 2001-01-24 | 2007-01-15 | Cadila Healthcare Ltd | Verfahren zur herstellung von clopidogrel |
ITMI20020933A1 (it) * | 2002-05-03 | 2003-11-03 | Danimite Dipharma S P A | Procedimento per la sintesi di clopidogrel |
BRPI0510008A (pt) * | 2004-04-20 | 2007-09-18 | Sanofi Aventis | sal de clopidogrel e formas polimórficas deste |
-
2006
- 2006-05-26 CN CNB2006100516843A patent/CN100396687C/zh active Active
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103044444A (zh) * | 2013-01-21 | 2013-04-17 | 上海现代哈森(商丘)药业有限公司 | 一种高纯度ⅰ型(+)-(s)-硫酸氢氯吡格雷的合成方法 |
CN103044444B (zh) * | 2013-01-21 | 2015-04-15 | 上海现代哈森(商丘)药业有限公司 | 一种高纯度ⅰ型(+)-(s)-硫酸氢氯吡格雷的合成方法 |
CN107118221A (zh) * | 2017-05-24 | 2017-09-01 | 常州制药厂有限公司 | 一种硫酸氢氯吡格雷晶型i制备方法 |
CN107118221B (zh) * | 2017-05-24 | 2021-09-07 | 常州制药厂有限公司 | 一种硫酸氢氯吡格雷晶型i制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN100396687C (zh) | 2008-06-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR20150053816A (ko) | 테노포비어 디소프록실의 결정형 및 그의 제조방법 | |
CN1027507C (zh) | 新的磺酰化合物的制备方法 | |
CN104230992A (zh) | 一种高纯度富马酸泰诺福韦酯的制备方法 | |
CN112898299B (zh) | 一种帕布昔利布中间体的制备方法 | |
JP2007516934A (ja) | (+)−(s)−クロピドグレル重硫酸塩形態−iの新規な製造方法 | |
CN1850827A (zh) | (+)-(s-)-氯吡格雷硫酸氢盐(i型)的制备方法 | |
CN1041918C (zh) | 芳基哌啶甲醇的制法 | |
JP2016531925A (ja) | ペメトレキセド製造のための中間体製造方法及びこれを用いて高純度ペメトレキセドを製造する方法 | |
CN1679586A (zh) | 含哌嗪环化合物的新型合成和结晶方法 | |
CN103012288B (zh) | 6-氯-1,3-二甲基脲嘧啶的制备方法 | |
CN103848768B (zh) | 一种甲氨基甲酰氯分解尾气氯化氢在杀螟丹合成中的应用方法 | |
CN108752184B (zh) | 一种sglt2抑制剂中间体的制备方法 | |
CN1319978C (zh) | 康布瑞汀化合物的制备方法 | |
CN104130149A (zh) | 一种3-(s)-氨基丁酸衍生物的回收利用方法 | |
CN112778094B (zh) | 一种高纯度四溴双酚a的制备工艺 | |
CN1821220A (zh) | 4-[(4-氧代-3-溴)丁基]苯甲酰-l-谷氨酸二乙酯及制备和应用 | |
CN112940022B (zh) | 一种二甲胺硼烷的制备方法 | |
KR101485418B1 (ko) | 고순도 미르타자핀의 제조방법 | |
CN117510367B (zh) | 头孢克肟侧链开环酸的制备方法 | |
CN101857600B (zh) | 一种7-苯乙酰氨基-3-甲基头孢烷酸的制备方法 | |
CN1882526A (zh) | 制备伏格列波糖的方法 | |
CN102089311A (zh) | 吗啡喃合成方法 | |
CN1032642C (zh) | 一种制取硫酸钾的改进方法 | |
CN1305876C (zh) | 制备高纯度头孢泊肟酯的方法 | |
CN104817600A (zh) | 一种二氢高红霉素的制备纯化方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation of (+) - (s -) - clopidogrel bisulfate (type I) Effective date of registration: 20210520 Granted publication date: 20080625 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISOAR PHARMACEUTICAL Co.,Ltd. Registration number: Y2021330000425 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20211223 Granted publication date: 20080625 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISOAR PHARMACEUTICAL Co.,Ltd. Registration number: Y2021330000425 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation of (+) - (s-) - clopidogrel bisulfate (type I) Effective date of registration: 20220527 Granted publication date: 20080625 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISOAR PHARMACEUTICAL Co.,Ltd. Registration number: Y2022330000812 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230912 Granted publication date: 20080625 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISOAR PHARMACEUTICAL Co.,Ltd. Registration number: Y2022330000812 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of (+) - (S -) - clopidogrel bisulfate (Type I) Effective date of registration: 20231124 Granted publication date: 20080625 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISOAR PHARMACEUTICAL Co.,Ltd. Registration number: Y2023330002795 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |