CN101376645B - 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 - Google Patents
碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 Download PDFInfo
- Publication number
- CN101376645B CN101376645B CN2007100453270A CN200710045327A CN101376645B CN 101376645 B CN101376645 B CN 101376645B CN 2007100453270 A CN2007100453270 A CN 2007100453270A CN 200710045327 A CN200710045327 A CN 200710045327A CN 101376645 B CN101376645 B CN 101376645B
- Authority
- CN
- China
- Prior art keywords
- formula
- preparation
- suc
- reaction
- compound
- 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.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 229930182555 Penicillin Natural products 0.000 title claims abstract description 8
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 title claims abstract description 8
- 229940049954 penicillin Drugs 0.000 title claims abstract description 8
- JUZNIMUFDBIJCM-ANEDZVCMSA-N Invanz Chemical compound O=C([C@H]1NC[C@H](C1)SC=1[C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)NC1=CC=CC(C(O)=O)=C1 JUZNIMUFDBIJCM-ANEDZVCMSA-N 0.000 title claims description 20
- 229960002770 ertapenem Drugs 0.000 title claims description 18
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 title claims 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 40
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract description 4
- 230000002194 synthesizing effect Effects 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 10
- 239000000543 intermediate Substances 0.000 claims description 9
- SDJHDRMYZQFJJO-UHFFFAOYSA-N ethanethioic s-acid;potassium Chemical compound [K].CC(S)=O SDJHDRMYZQFJJO-UHFFFAOYSA-N 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 239000002798 polar solvent Substances 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 12
- 238000009776 industrial production Methods 0.000 abstract description 2
- 229940041011 carbapenems Drugs 0.000 abstract 2
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 abstract 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000012141 concentrate Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 238000003809 water extraction Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 150000007530 organic bases Chemical class 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000001476 alcoholic effect Effects 0.000 description 6
- 238000003810 ethyl acetate extraction Methods 0.000 description 6
- 238000012797 qualification Methods 0.000 description 6
- CGIHPACLZJDCBQ-UHFFFAOYSA-N acibenzolar Chemical compound SC(=O)C1=CC=CC2=C1SN=N2 CGIHPACLZJDCBQ-UHFFFAOYSA-N 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012454 non-polar solvent Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- -1 diethyl propyl group Chemical group 0.000 description 2
- OTTZHAVKAVGASB-UHFFFAOYSA-N hept-2-ene Chemical compound CCCCC=CC OTTZHAVKAVGASB-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical compound OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000004567 concrete Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Natural products CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 1
- PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 229940054114 invanz Drugs 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical group COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- ZBOGUDPFEVIZIQ-UHFFFAOYSA-N toluene;dihydrochloride Chemical group Cl.Cl.CC1=CC=CC=C1 ZBOGUDPFEVIZIQ-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (9)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2007100453270A CN101376645B (zh) | 2007-08-28 | 2007-08-28 | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2007100453270A CN101376645B (zh) | 2007-08-28 | 2007-08-28 | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101376645A CN101376645A (zh) | 2009-03-04 |
CN101376645B true CN101376645B (zh) | 2010-12-22 |
Family
ID=40420390
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2007100453270A Expired - Fee Related CN101376645B (zh) | 2007-08-28 | 2007-08-28 | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101376645B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015087245A1 (en) | 2013-12-11 | 2015-06-18 | Unimark Remedies Ltd. | Process for preparation of ertapenem and salts thereof |
-
2007
- 2007-08-28 CN CN2007100453270A patent/CN101376645B/zh not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN101376645A (zh) | 2009-03-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DK170073B1 (da) | Analogifremgangsmåde til fremstilling af carbapenemderivater | |
EP0182213A1 (en) | Carbapenem compounds and production thereof | |
JP2007520453A5 (zh) | ||
TW201141867A (en) | Improved process for the preparation of carbapenem using carbapenem intermediates and recovery of carbapenem | |
CN101376643B (zh) | 一种碳青霉烯类青霉素厄他培南的中间体的制备方法 | |
CN101376641B (zh) | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 | |
CN101376645B (zh) | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 | |
CN102558181A (zh) | 一种碳青霉烯抗生素的制备方法 | |
CN101376642B (zh) | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 | |
CN101376633B (zh) | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 | |
CN101137621A (zh) | 吡咯烷衍生物中间体及其制备方法和用途 | |
CN101376644B (zh) | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 | |
BG60499B2 (bg) | Бета-лактамови съединения и метод за получаванетоим | |
CN101575298A (zh) | 一种制备手性医药中间体2-氨基-1-苯乙醇的方法 | |
CN101376636A (zh) | 碳青霉烯类青霉素厄他培南的中间体及其制备方法和应用 | |
CN103059046B (zh) | 一种法罗培南的制备方法 | |
JPS5921693A (ja) | 抗菌性ペネム誘導体 | |
CN102617612B (zh) | 比阿培南b型结晶 | |
CN101848911A (zh) | 碳青霉烯类抗生素的合成中间体的酸加成盐及其制备方法 | |
CN101885727A (zh) | 一种制备帕尼培南的方法 | |
KR100930586B1 (ko) | 2-아릴메틸아제티딘-카바페넴-3-카복실산 에스테르 유도체,이의 제조방법 및 이를 포함하는 약학 조성물 | |
CN101367830B (zh) | 一种硫霉素衍生物的合成方法 | |
CN101367831B (zh) | 用于制备碳青霉烯类抗生素的中间体及其制备方法 | |
JPH0670059B2 (ja) | フルオロアルキル化カルバペネム中間体 | |
JP2008303143A (ja) | 連続化反応によるカルバぺネム誘導体の製法 |
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 | ||
ASS | Succession or assignment of patent right |
Owner name: WUHAN QIRUI PHARMACEUTICALS CO., LTD. |
|
C41 | Transfer of patent application or patent right or utility model | ||
C53 | Correction of patent for invention or patent application | ||
CB03 | Change of inventor or designer information |
Inventor after: Lu Yang Inventor after: Dan Xiaoyan Inventor after: Shi Huilin Inventor after: Wang Chaodong Inventor after: Liu Yong Inventor before: Lu Yang Inventor before: Dan Xiaoyan Inventor before: Shi Huilin |
|
COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: LU YANG DAN XIAOYAN SHI HUILIN TO: LU YANG DAN XIAOYAN SHI HUILIN WANG ZHAODONG LIU YONG |
|
TR01 | Transfer of patent right |
Effective date of registration: 20110511 Address after: 200040 Beijing West Road, Shanghai, No. 1320 Co-patentee after: Wuhan Qirui Pharmaceuticals Co., Ltd. Patentee after: Shanghai Institute of pharmaceutical industry Address before: 200040 Beijing West Road, Shanghai, No. 1320 Patentee before: Shanghai Institute of pharmaceutical industry |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101222 Termination date: 20200828 |
|
CF01 | Termination of patent right due to non-payment of annual fee |