CN114409620A - 一种盐酸胺碘酮中间体的制备方法 - Google Patents
一种盐酸胺碘酮中间体的制备方法 Download PDFInfo
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- CN114409620A CN114409620A CN202210149371.0A CN202210149371A CN114409620A CN 114409620 A CN114409620 A CN 114409620A CN 202210149371 A CN202210149371 A CN 202210149371A CN 114409620 A CN114409620 A CN 114409620A
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- China
- Prior art keywords
- butylbenzofuran
- methoxyphenyl
- preparation
- reaction
- methanone
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 229960003234 amiodarone hydrochloride Drugs 0.000 title claims abstract description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 90
- ZECBGDFBAKHQFF-UHFFFAOYSA-N (2-butyl-1-benzofuran-3-yl)-(4-methoxyphenyl)methanone Chemical compound CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(OC)C=C1 ZECBGDFBAKHQFF-UHFFFAOYSA-N 0.000 claims abstract description 48
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 43
- OVJKFJDEVKABNF-UHFFFAOYSA-N 2-butyl-1-benzofuran Chemical compound C1=CC=C2OC(CCCC)=CC2=C1 OVJKFJDEVKABNF-UHFFFAOYSA-N 0.000 claims abstract description 34
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 42
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 238000010791 quenching Methods 0.000 claims description 17
- 230000000171 quenching effect Effects 0.000 claims description 17
- 238000005406 washing Methods 0.000 claims description 16
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 14
- 239000012044 organic layer Substances 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 11
- 238000001816 cooling Methods 0.000 claims description 6
- 238000001704 evaporation Methods 0.000 claims description 6
- 239000010410 layer Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 230000007613 environmental effect Effects 0.000 abstract description 7
- 238000009776 industrial production Methods 0.000 abstract description 6
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 239000002699 waste material Substances 0.000 abstract description 3
- 230000000052 comparative effect Effects 0.000 description 34
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 10
- 238000002156 mixing Methods 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 239000012535 impurity Substances 0.000 description 7
- ZHGKQUXXASLVQQ-UHFFFAOYSA-N (2-Butylbenzofuran-3-yl)(4-hydroxyphenyl)ketone Chemical compound CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 ZHGKQUXXASLVQQ-UHFFFAOYSA-N 0.000 description 6
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- CNCBKULTPJTRNN-UHFFFAOYSA-N 5-(1-benzofuran-2-yl)-6-butyl-4-[2-(diethylamino)ethoxy]-3,5-diiodocyclohexa-1,3-diene-1-carbaldehyde hydrochloride Chemical compound CCCCC1C(=CC(=C(C1(C2=CC3=CC=CC=C3O2)I)OCCN(CC)CC)I)C=O.Cl CNCBKULTPJTRNN-UHFFFAOYSA-N 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 206010003662 Atrial flutter Diseases 0.000 description 1
- 206010052895 Coronary artery insufficiency Diseases 0.000 description 1
- NEAPKZHDYMQZCB-UHFFFAOYSA-N N-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]ethyl]-2-oxo-3H-1,3-benzoxazole-6-carboxamide Chemical compound C1CN(CCN1CCNC(=O)C2=CC3=C(C=C2)NC(=O)O3)C4=CN=C(N=C4)NC5CC6=CC=CC=C6C5 NEAPKZHDYMQZCB-UHFFFAOYSA-N 0.000 description 1
- 208000008376 Pre-Excitation Syndromes Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000003734 Supraventricular Tachycardia Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 208000008510 paroxysmal tachycardia Diseases 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Claims (8)
Priority Applications (1)
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CN202210149371.0A CN114409620A (zh) | 2022-02-18 | 2022-02-18 | 一种盐酸胺碘酮中间体的制备方法 |
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CN202210149371.0A CN114409620A (zh) | 2022-02-18 | 2022-02-18 | 一种盐酸胺碘酮中间体的制备方法 |
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CN114409620A true CN114409620A (zh) | 2022-04-29 |
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CN202210149371.0A Pending CN114409620A (zh) | 2022-02-18 | 2022-02-18 | 一种盐酸胺碘酮中间体的制备方法 |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102321058A (zh) * | 2011-07-20 | 2012-01-18 | 北京赛科药业有限责任公司 | 一种合成盐酸决奈达隆的方法 |
CN104926900A (zh) * | 2014-03-22 | 2015-09-23 | 上海创诺制药有限公司 | 一种制备式i所示的卡培他滨中间体的方法 |
CN106137963A (zh) * | 2016-07-27 | 2016-11-23 | 武汉科福新药有限责任公司 | 抗心律失常药物脂肪乳注射液及其制备方法 |
CN107382925A (zh) * | 2017-07-20 | 2017-11-24 | 烟台万润药业有限公司 | 一种盐酸胺碘酮的制备方法 |
CN109988132A (zh) * | 2019-04-18 | 2019-07-09 | 浙江三门恒康制药有限公司 | 一种盐酸胺碘酮的制备方法 |
CN110845443A (zh) * | 2019-12-11 | 2020-02-28 | 嘉实(湖南)医药科技有限公司 | 一种制备高纯度盐酸托哌酮的方法 |
-
2022
- 2022-02-18 CN CN202210149371.0A patent/CN114409620A/zh active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102321058A (zh) * | 2011-07-20 | 2012-01-18 | 北京赛科药业有限责任公司 | 一种合成盐酸决奈达隆的方法 |
CN104926900A (zh) * | 2014-03-22 | 2015-09-23 | 上海创诺制药有限公司 | 一种制备式i所示的卡培他滨中间体的方法 |
CN106137963A (zh) * | 2016-07-27 | 2016-11-23 | 武汉科福新药有限责任公司 | 抗心律失常药物脂肪乳注射液及其制备方法 |
CN107382925A (zh) * | 2017-07-20 | 2017-11-24 | 烟台万润药业有限公司 | 一种盐酸胺碘酮的制备方法 |
CN109988132A (zh) * | 2019-04-18 | 2019-07-09 | 浙江三门恒康制药有限公司 | 一种盐酸胺碘酮的制备方法 |
CN110845443A (zh) * | 2019-12-11 | 2020-02-28 | 嘉实(湖南)医药科技有限公司 | 一种制备高纯度盐酸托哌酮的方法 |
Non-Patent Citations (2)
Title |
---|
HAO CHEN等: "Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》, vol. 46, pages 128160 - 128165 * |
JIN ZHANG等: "Structure-Guided Design of a Small-Molecule Activator of Sirtuin-3 that Modulates Autophagy in Triple Negative Breast Cancer", 《JOURNAL OF MEDICINAL CHEMISTRY》, vol. 64, pages 14206 * |
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Effective date of registration: 20240219 Address after: 246004 No. 58, xiahong Road, high tech Industrial Development Zone, Anqing City, Anhui Province Applicant after: Anhui Puli Pharmaceutical Co.,Ltd. Country or region after: China Address before: 571127 Guilin Ocean Economic Development Zone, Meilan District, Haikou City, Hainan Province Applicant before: HAINAN POLY PHARM. Co.,Ltd. Country or region before: China Applicant before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Applicant before: Anhui Puli Pharmaceutical Co.,Ltd. |
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