CN103130700B - 一种阿折地平中间体的制备方法 - Google Patents
一种阿折地平中间体的制备方法 Download PDFInfo
- Publication number
- CN103130700B CN103130700B CN201310081090.7A CN201310081090A CN103130700B CN 103130700 B CN103130700 B CN 103130700B CN 201310081090 A CN201310081090 A CN 201310081090A CN 103130700 B CN103130700 B CN 103130700B
- Authority
- CN
- China
- Prior art keywords
- benzhydryl
- reaction
- acid
- azetidine
- imino
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- ZKFQEACEUNWPMT-UHFFFAOYSA-N Azelnidipine Chemical compound CC(C)OC(=O)C1=C(C)NC(N)=C(C(=O)OC2CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZKFQEACEUNWPMT-UHFFFAOYSA-N 0.000 title abstract description 16
- 229950004646 azelnidipine Drugs 0.000 title abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- 239000002904 solvent Substances 0.000 claims abstract description 11
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims abstract description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 15
- 238000001816 cooling Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000001704 evaporation Methods 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 4
- MMAJXKGUZYDTHV-UHFFFAOYSA-N 1-benzhydrylazetidin-3-ol Chemical compound C1C(O)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 MMAJXKGUZYDTHV-UHFFFAOYSA-N 0.000 claims description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 3
- 239000005695 Ammonium acetate Substances 0.000 claims description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 3
- 229940043376 ammonium acetate Drugs 0.000 claims description 3
- 235000019257 ammonium acetate Nutrition 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- KSZGPBFUBSHVTO-UHFFFAOYSA-N (1-benzhydrylazetidin-3-yl) 2-cyanoacetate Chemical compound C1C(OC(CC#N)=O)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 KSZGPBFUBSHVTO-UHFFFAOYSA-N 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000011345 viscous material Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 20
- 238000006386 neutralization reaction Methods 0.000 abstract description 9
- 238000005886 esterification reaction Methods 0.000 abstract description 6
- 238000003482 Pinner synthesis reaction Methods 0.000 abstract description 5
- 230000032050 esterification Effects 0.000 abstract description 4
- 150000001409 amidines Chemical class 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- DCGRISOXIFQLPD-UHFFFAOYSA-N acetic acid;(1-benzhydrylazetidin-3-yl) 3-amino-3-iminopropanoate Chemical compound CC(O)=O.C1C(OC(=O)CC(=N)N)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 DCGRISOXIFQLPD-UHFFFAOYSA-N 0.000 abstract 2
- AVUDXLOVIBJFQA-UHFFFAOYSA-N 1-benzhydrylazetidin-3-one Chemical compound C1C(=O)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 AVUDXLOVIBJFQA-UHFFFAOYSA-N 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 150000007530 organic bases Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- -1 ester acetate Chemical class 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000002866 dihydropyridine calcium channel blocker Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003513 tertiary aromatic amines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Claims (1)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310081090.7A CN103130700B (zh) | 2013-03-14 | 2013-03-14 | 一种阿折地平中间体的制备方法 |
PCT/CN2014/073222 WO2014139410A1 (zh) | 2013-03-14 | 2014-03-11 | 一种阿折地平中间体的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310081090.7A CN103130700B (zh) | 2013-03-14 | 2013-03-14 | 一种阿折地平中间体的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103130700A CN103130700A (zh) | 2013-06-05 |
CN103130700B true CN103130700B (zh) | 2015-04-29 |
Family
ID=48491205
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310081090.7A Active CN103130700B (zh) | 2013-03-14 | 2013-03-14 | 一种阿折地平中间体的制备方法 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN103130700B (zh) |
WO (1) | WO2014139410A1 (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103130700B (zh) * | 2013-03-14 | 2015-04-29 | 沈阳中海药业有限公司 | 一种阿折地平中间体的制备方法 |
CN104860855B (zh) * | 2014-12-08 | 2017-06-16 | 宁夏紫光天化蛋氨酸有限责任公司 | 一种高纯度的d,l‑2‑羟基‑4‑甲硫基丁酸酯的制备方法 |
CN105949102A (zh) * | 2016-06-20 | 2016-09-21 | 许昌豪丰化学科技有限公司 | 一种阿折地平中间体的生产方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101475521A (zh) * | 2008-11-13 | 2009-07-08 | 青岛黄海制药有限责任公司 | 1-二苯甲基-3-氮杂环丁烷基脒基乙酸酯的乙酸盐的合成方法 |
CN102453023A (zh) * | 2010-10-21 | 2012-05-16 | 大丰市天生药业有限公司 | 一种阿折地平生产工艺 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3491506B2 (ja) * | 1997-10-14 | 2004-01-26 | 宇部興産株式会社 | ジヒドロピリジン誘導体の製造法 |
CN103509003A (zh) * | 2012-06-27 | 2014-01-15 | 威海威太医药技术开发有限公司 | 一种阿折地平的制备方法 |
CN103130700B (zh) * | 2013-03-14 | 2015-04-29 | 沈阳中海药业有限公司 | 一种阿折地平中间体的制备方法 |
-
2013
- 2013-03-14 CN CN201310081090.7A patent/CN103130700B/zh active Active
-
2014
- 2014-03-11 WO PCT/CN2014/073222 patent/WO2014139410A1/zh active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101475521A (zh) * | 2008-11-13 | 2009-07-08 | 青岛黄海制药有限责任公司 | 1-二苯甲基-3-氮杂环丁烷基脒基乙酸酯的乙酸盐的合成方法 |
CN102453023A (zh) * | 2010-10-21 | 2012-05-16 | 大丰市天生药业有限公司 | 一种阿折地平生产工艺 |
Non-Patent Citations (2)
Title |
---|
阿折地平的合成及其结晶的研究;陈国斌,等;《化学工业与工程》;20090131;第26卷(第1期);第15-18页 * |
阿折地平的合成及手性拆分方法研究;张恺;《河北医科大学硕士学位论文》;20071215;第15-16页、第20-21页、第25页、第28页 * |
Also Published As
Publication number | Publication date |
---|---|
WO2014139410A1 (zh) | 2014-09-18 |
CN103130700A (zh) | 2013-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2645362C (en) | Synthesis of acylaminoalkenylene amides useful as substance p antagonists | |
EA018227B1 (ru) | Способ получения дабигатрана и его промежуточные соединения | |
CN110590635A (zh) | 左乙拉西坦及其中间体的制备方法 | |
CN103130700B (zh) | 一种阿折地平中间体的制备方法 | |
WO2001000571A1 (en) | Process for preparing substituted cyclopentane derivatives and novel crystalline structures thereof | |
AU2011363636B2 (en) | Process for the production of a pemetrexed salt | |
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 | |
CN110498771B (zh) | 一种制备恶拉戈利的中间体的方法 | |
WO2009062036A2 (en) | Processes for preparing levocetirizine and pharmaceutically acceptable salts thereof | |
CN107235913B (zh) | 工业规模高效制造优质氟班色林的方法 | |
US8952148B2 (en) | Process for the preparation of taurolidine and its intermediates thereof | |
EP3081554A1 (en) | Method for preparing silodosin and intermediate thereof | |
CN109836424B (zh) | 一种环保型茶碱钠盐甲基化制备咖啡因的方法 | |
JP5640283B2 (ja) | ピリミジン誘導体の調製プロセス | |
KR102518994B1 (ko) | Azd5363의 제조 방법 및 그에 사용되는 신규 중간체 | |
CN112272665A (zh) | 制备立他司特的方法 | |
CN110964013B (zh) | 利格列汀及其中间体的制备方法 | |
CN118206567B (zh) | 一种稠环化合物的制备方法 | |
CN115477653B (zh) | 一种曲拉西利关键中间体及曲拉西利的制备方法 | |
CN113636980B (zh) | 一种右丙亚胺的制备方法 | |
CN103183643A (zh) | 一种利吡韦林中间体及其制备方法和应用 | |
CN116768901A (zh) | 一种培美曲塞二钠的制备方法 | |
CN111620807A (zh) | 一种盐酸左旋米那普仑杂质的制备方法 | |
WO2007062675A1 (en) | Method for producing metal salts of losartan | |
WO2008026527A1 (fr) | Procédé de fabrication d'un dérivé de 3-cyanopyrrolidine ou d'un de ses sels |
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 | ||
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20151109 Address after: South Street of Shenhe District of Shenyang City, Liaoning province 110016 Lane 129 No. 28 Patentee after: Shengyang Zhonghai Biological Technology Development Co., Ltd. Address before: 110300 Dong Daying Industrial Park, Xinmin, Liaoning, Shenyang Patentee before: Shenyang J&Health Pharmaceutical Co., Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20170207 Address after: Two street 100176 Beijing Daxing District Yizhuang Development Zone No. 8 Han Liangshui River Bay 7 Building Enterprises Patentee after: BEIJING VOBAN PHARMACEUTICAL CO., LTD. Address before: South Street of Shenhe District of Shenyang City, Liaoning province 110016 Lane 129 No. 28 Patentee before: Shengyang Zhonghai Biological Technology Development Co., Ltd. |