CN101899035B - 一种高纯度伊马替尼的制备方法 - Google Patents
一种高纯度伊马替尼的制备方法 Download PDFInfo
- Publication number
- CN101899035B CN101899035B CN2010102740021A CN201010274002A CN101899035B CN 101899035 B CN101899035 B CN 101899035B CN 2010102740021 A CN2010102740021 A CN 2010102740021A CN 201010274002 A CN201010274002 A CN 201010274002A CN 101899035 B CN101899035 B CN 101899035B
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- CN
- China
- Prior art keywords
- pyridine
- methyl
- solvent
- water
- amino
- 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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- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 229960002411 imatinib Drugs 0.000 title claims abstract description 25
- 239000005517 L01XE01 - Imatinib Substances 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 239000013078 crystal Substances 0.000 claims abstract description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 9
- 239000012074 organic phase Substances 0.000 claims abstract description 8
- 150000002191 fatty alcohols Chemical class 0.000 claims abstract description 6
- 239000012535 impurity Substances 0.000 claims abstract description 6
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims abstract description 3
- 239000011230 binding agent Substances 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- ABOLPUDOABZSNW-UHFFFAOYSA-N N1CCNCC1.CC1=C(C=C(C(=O)O)C=C1)C(=O)O Chemical compound N1CCNCC1.CC1=C(C=C(C(=O)O)C=C1)C(=O)O ABOLPUDOABZSNW-UHFFFAOYSA-N 0.000 claims description 11
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 8
- 239000008346 aqueous phase Substances 0.000 claims description 7
- 238000005191 phase separation Methods 0.000 claims description 7
- 238000001556 precipitation Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract 3
- 239000012071 phase Substances 0.000 abstract 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract 1
- ZOUYJERDNYMHCS-UHFFFAOYSA-N benzoyl chloride;dihydrochloride Chemical compound Cl.Cl.ClC(=O)C1=CC=CC=C1 ZOUYJERDNYMHCS-UHFFFAOYSA-N 0.000 abstract 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- 229960000582 mepyramine Drugs 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- 239000005457 ice water Substances 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000010792 warming Methods 0.000 description 10
- 238000011084 recovery Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000013019 agitation Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000010606 normalization Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000000967 suction filtration Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 208000019838 Blood disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 201000008806 mesenchymal cell neoplasm Diseases 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
Description
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102740021A CN101899035B (zh) | 2010-09-03 | 2010-09-03 | 一种高纯度伊马替尼的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102740021A CN101899035B (zh) | 2010-09-03 | 2010-09-03 | 一种高纯度伊马替尼的制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101899035A CN101899035A (zh) | 2010-12-01 |
| CN101899035B true CN101899035B (zh) | 2012-09-05 |
Family
ID=43224996
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102740021A Active CN101899035B (zh) | 2010-09-03 | 2010-09-03 | 一种高纯度伊马替尼的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101899035B (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102796079B (zh) * | 2011-05-27 | 2016-06-29 | 江苏豪森药业集团有限公司 | 一种甲磺酸氟马替尼的制备方法 |
| CN103848813B (zh) * | 2012-12-04 | 2016-08-03 | 北大方正集团有限公司 | 伊马替尼的制备方法 |
| CN103910711A (zh) * | 2014-03-24 | 2014-07-09 | 福建天泉药业股份有限公司 | 一种伊马替尼游离碱晶型及其制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2398565A (en) * | 2003-02-18 | 2004-08-25 | Cipla Ltd | Imatinib preparation and salts |
| WO2008051597A1 (en) * | 2006-10-26 | 2008-05-02 | Sicor Inc. | Process for the preparation of imatinib |
-
2010
- 2010-09-03 CN CN2010102740021A patent/CN101899035B/zh active Active
Non-Patent Citations (1)
| Title |
|---|
| 李铭东 等.甲磺酸伊马替尼的合成.《中国药学杂志》.2008,第43卷(第3期),第228-229页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101899035A (zh) | 2010-12-01 |
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Denomination of invention: Preparation method of high-purity imatinib Effective date of registration: 20140320 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000178 |
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Date of cancellation: 20141030 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000178 |
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Denomination of invention: Preparation method of high-purity imatinib Effective date of registration: 20141031 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000913 |
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Date of cancellation: 20151021 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000913 |
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Denomination of invention: Preparation method of high-purity imatinib Effective date of registration: 20151021 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2015990000906 |
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Date of cancellation: 20161017 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2015990000906 |
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Denomination of invention: Preparation method of high-purity imatinib Effective date of registration: 20161017 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2016990000880 |
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Date of cancellation: 20171018 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2016990000880 |
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Denomination of invention: Preparation method of high-purity imatinib Effective date of registration: 20171018 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2017990000966 |
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Date of cancellation: 20181018 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2017990000966 |
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Denomination of invention: Preparation method of high-purity imatinib Effective date of registration: 20181018 Granted publication date: 20120905 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2018990000977 |
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