CN101074217A - 通过制备色谱分离得到高纯度恩替卡韦关键中间体的方法 - Google Patents
通过制备色谱分离得到高纯度恩替卡韦关键中间体的方法 Download PDFInfo
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- CN101074217A CN101074217A CN 200710090303 CN200710090303A CN101074217A CN 101074217 A CN101074217 A CN 101074217A CN 200710090303 CN200710090303 CN 200710090303 CN 200710090303 A CN200710090303 A CN 200710090303A CN 101074217 A CN101074217 A CN 101074217A
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- 238000000926 separation method Methods 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 24
- 229960000980 entecavir Drugs 0.000 claims description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 claims description 20
- 230000005526 G1 to G0 transition Effects 0.000 claims description 19
- 238000013375 chromatographic separation Methods 0.000 claims description 18
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- 239000000377 silicon dioxide Substances 0.000 claims description 8
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- 238000004237 preparative chromatography Methods 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
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- 229960000935 dehydrated alcohol Drugs 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 14
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- 239000012535 impurity Substances 0.000 description 8
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
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- 230000011218 segmentation Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
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- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- UYLWKSJTHLRFBX-UHFFFAOYSA-N purin-6-one Chemical compound O=C1N=CN=C2N=CN=C12 UYLWKSJTHLRFBX-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
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- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
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- Treatment Of Liquids With Adsorbents In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
色谱柱的分离比 | 含目标异构体的混合物的量 | 相对纯度 |
1.67 | 80mg | 98.3% |
色谱柱分离比 | 目标异构体的量 | 相对纯度 |
1.7 | 59.5mg | 99.1% |
色谱柱分离比 | 纯化后样品的量 | 相对纯度 |
1.7 | 39.9mg | 99% |
色谱柱分离比 | 目标异构体的量 | 相对纯度 |
1.7 | 33.1mg | 99% |
Claims (25)
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CN2007100903037A CN101074217B (zh) | 2007-04-04 | 2007-04-04 | 通过制备色谱分离得到高纯度恩替卡韦关键中间体的方法 |
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CN2007100903037A CN101074217B (zh) | 2007-04-04 | 2007-04-04 | 通过制备色谱分离得到高纯度恩替卡韦关键中间体的方法 |
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Publication Number | Publication Date |
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CN101074217A true CN101074217A (zh) | 2007-11-21 |
CN101074217B CN101074217B (zh) | 2010-11-24 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102305837A (zh) * | 2011-05-21 | 2012-01-04 | 江苏诺泰制药技术有限公司 | 控制恩替卡韦及其中间体有关物质和异构体含量的检测方法 |
CN105891400A (zh) * | 2015-07-29 | 2016-08-24 | 福建广生堂药业股份有限公司 | 一种检测恩替卡韦关键中间体的方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5206244A (en) * | 1990-10-18 | 1993-04-27 | E. R. Squibb & Sons, Inc. | Hydroxymethyl (methylenecyclopentyl) purines and pyrimidines |
IN2012DN00606A (zh) * | 2002-12-11 | 2015-06-12 | Bristol Mayers Squibb Company | |
CN100379736C (zh) * | 2005-05-13 | 2008-04-09 | 上海仲夏化学有限公司 | 恩替卡韦的制备方法 |
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- 2007-04-04 CN CN2007100903037A patent/CN101074217B/zh not_active Expired - Fee Related
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102305837A (zh) * | 2011-05-21 | 2012-01-04 | 江苏诺泰制药技术有限公司 | 控制恩替卡韦及其中间体有关物质和异构体含量的检测方法 |
CN105891400A (zh) * | 2015-07-29 | 2016-08-24 | 福建广生堂药业股份有限公司 | 一种检测恩替卡韦关键中间体的方法 |
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Application publication date: 20071121 Assignee: Beijing Xinlingxian Medical Technology Development Co., Ltd. Assignor: Beijing JHYB Pharmaceutical Technology Co., Ltd. Contract record no.: 2012990000558 Denomination of invention: Method for obtaining endicawil critical intermediate by chromatogram separation Granted publication date: 20101124 License type: Exclusive License Record date: 20120802 Application publication date: 20071121 Assignee: Beijing Xinlingxian Medical Technology Development Co., Ltd. Assignor: Beijing JHYB Pharmaceutical Technology Co., Ltd. Contract record no.: 2012990000558 Denomination of invention: Method for obtaining endicawil critical intermediate by chromatogram separation Granted publication date: 20101124 License type: Exclusive License Record date: 20120802 |
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