CN103183663B - 一种阿折地平的制备方法 - Google Patents
一种阿折地平的制备方法 Download PDFInfo
- Publication number
- CN103183663B CN103183663B CN201310115497.7A CN201310115497A CN103183663B CN 103183663 B CN103183663 B CN 103183663B CN 201310115497 A CN201310115497 A CN 201310115497A CN 103183663 B CN103183663 B CN 103183663B
- Authority
- CN
- China
- Prior art keywords
- reaction
- preparation
- compound
- azelnidipine
- method described
- 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
- 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 claims abstract description 19
- 229950004646 azelnidipine Drugs 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 229910021529 ammonia Inorganic materials 0.000 claims description 15
- -1 amidine compound Chemical class 0.000 claims description 11
- 239000007789 gas Substances 0.000 claims description 9
- 238000005915 ammonolysis reaction Methods 0.000 claims description 8
- 229940126214 compound 3 Drugs 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 5
- 239000005695 Ammonium acetate Substances 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 229940043376 ammonium acetate Drugs 0.000 claims description 5
- 235000019257 ammonium acetate Nutrition 0.000 claims description 5
- 229940125898 compound 5 Drugs 0.000 claims description 5
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 5
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 229940125904 compound 1 Drugs 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 2
- 238000005349 anion exchange Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 239000002220 antihypertensive agent Substances 0.000 abstract description 2
- 229940127088 antihypertensive drug Drugs 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 2
- 150000001409 amidines Chemical class 0.000 abstract 1
- 239000007810 chemical reaction solvent Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 10
- 238000013019 agitation Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 238000010792 warming Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000009413 insulation Methods 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- CJEPGJMSWITLJD-UHFFFAOYSA-O C/[NH+]=C(\CC(OC(C1)CN1C(c1ccccc1)c1ccccc1)=O)/N Chemical compound C/[NH+]=C(\CC(OC(C1)CN1C(c1ccccc1)c1ccccc1)=O)/N CJEPGJMSWITLJD-UHFFFAOYSA-O 0.000 description 1
- XZKRXPZXQLARHH-CLTKARDFSA-N C=C/C=C\c1ccccc1 Chemical compound C=C/C=C\c1ccccc1 XZKRXPZXQLARHH-CLTKARDFSA-N 0.000 description 1
- PJIJVZQBOLNCON-UHFFFAOYSA-N CN(C1)CC1OC(CC#N)=O Chemical compound CN(C1)CC1OC(CC#N)=O PJIJVZQBOLNCON-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 238000010959 commercial synthesis reaction Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 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
- 229960004756 ethanol Drugs 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000002045 lasting effect Effects 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
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- GVIIRWAJDFKJMJ-UHFFFAOYSA-N propan-2-yl 3-oxobutanoate Chemical compound CC(C)OC(=O)CC(C)=O GVIIRWAJDFKJMJ-UHFFFAOYSA-N 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims (2)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310115497.7A CN103183663B (zh) | 2013-03-25 | 2013-03-25 | 一种阿折地平的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310115497.7A CN103183663B (zh) | 2013-03-25 | 2013-03-25 | 一种阿折地平的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103183663A CN103183663A (zh) | 2013-07-03 |
CN103183663B true CN103183663B (zh) | 2017-01-25 |
Family
ID=48675140
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310115497.7A Active CN103183663B (zh) | 2013-03-25 | 2013-03-25 | 一种阿折地平的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103183663B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106588736A (zh) * | 2016-12-13 | 2017-04-26 | 威海迪素制药有限公司 | 一种阿折地平中间体乙酸脒的制备方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
-
2013
- 2013-03-25 CN CN201310115497.7A patent/CN103183663B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 (1)
Title |
---|
阿折地平的合成及手性拆分方法研究;张恺;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20071215(第06期);第E079-13页 * |
Also Published As
Publication number | Publication date |
---|---|
CN103183663A (zh) | 2013-07-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102190616B (zh) | 一种氘代的ω-二苯基脲的合成及生产的方法和工艺 | |
CN104024262B (zh) | 埃克替尼和盐酸埃克替尼的制备方法及其中间体 | |
CN110194776A (zh) | 一种瑞卢戈利的合成方法 | |
CN104945299B (zh) | 一种维格列汀的高效合成方法 | |
CN105153122A (zh) | [(吲哚-3-基)嘧啶-2-基]氨基苯基丙-2-烯酰胺衍生物及盐、制备方法、应用 | |
CN102417491A (zh) | 以10-去乙酰基-巴卡丁iii为原料制备卡巴他赛的方法 | |
CN102491918B (zh) | 一种丙氨酰谷氨酰胺化合物及其制法 | |
CN106349245A (zh) | 一种磷酸西格列汀杂质及其制备方法和用途 | |
CN107311875A (zh) | 重酒石酸间羟胺的合成方法 | |
CN105566215A (zh) | 一种瑞戈非尼的制备方法 | |
CN104826544B (zh) | 含有偶氮苯光敏基团的脂肽分子表面活性剂及其合成方法 | |
CN103183663B (zh) | 一种阿折地平的制备方法 | |
CN105367470A (zh) | 一种维格列汀的制备方法 | |
CN103897004B (zh) | 一种卡培他滨的合成方法 | |
CN103373960B (zh) | 一种托伐普坦中间体及其制备方法 | |
CN104478974B (zh) | 一种20,23-二哌啶基-5-o-碳霉胺糖基-泰乐内酯的合成方法 | |
CN108017561A (zh) | 一种精制卡谷氨酸的方法 | |
CN105523985A (zh) | 一种维格列汀的制备方法 | |
CN110437083A (zh) | 重酒石酸间羟胺对映异构体的合成方法 | |
CN102464661A (zh) | 一种5,6,7,8-四氢-咪唑并[1,5-a]吡嗪-1-羧酸乙酯的制备方法 | |
CN105085531B (zh) | 一种西格列汀杂质合成方法 | |
CN102584804B (zh) | 一种三苯甲基奥美沙坦酯脱保护基制备奥美沙坦酯的工艺 | |
CN104774197B (zh) | 一种苯并咪唑衍生物的制备方法 | |
CN105924400B (zh) | 阿齐沙坦杂质a和b的制备方法 | |
CN107129472B (zh) | 一种制备乙酰唑胺中间体的工艺 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20161227 Address after: Economic and Technological Development Zone of Shandong Province, Weihai City, Gushan Town, 264209 No. 18 South Road, No. 19 North Road, No. 3 East Road, the west five Applicant after: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. Applicant after: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Address before: Economic and Technological Development Zone of Shandong Province, Weihai City, Gushan Town, 264209 No. 18 South Road, No. 19 North Road, No. 3 East Road, the west five Applicant before: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. Applicant before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Applicant before: Weihai Weitai Pharmaceutical Technology Development Co.,Ltd. |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20191106 Address after: 264205 Guangzhou East Road South and an East Road East, Wendeng economic and Technological Development Zone, Weihai City, Shandong Province Co-patentee after: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Co-patentee after: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Address before: Economic and Technological Development Zone of Shandong Province, Weihai City, Gushan Town, 264209 No. 18 South Road, No. 19 North Road, No. 3 East Road, the west five Co-patentee before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Patentee before: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20210611 Address after: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Address before: 264205 Wendeng economic and Technological Development Zone, Weihai City, Shandong Province Patentee before: Dijia Pharmaceutical Group Co.,Ltd. Patentee before: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. Patentee before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. |
|
CP02 | Change in the address of a patent holder | ||
CP02 | Change in the address of a patent holder |
Address after: 264205 268 Tianrun Road, Wendeng economic and Technological Development Zone, Weihai, Shandong Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Address before: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Patentee before: Dijia Pharmaceutical Group Co.,Ltd. |
|
CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: No. 268, Tianrun Road, Wendeng Economic and Technological Development Zone, Weihai City, Shandong Province, 264200 Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Address before: 264205 268 Tianrun Road, Wendeng economic and Technological Development Zone, Weihai, Shandong Patentee before: Dijia Pharmaceutical Group Co.,Ltd. |