JP5065020B2 - レボフロキサシンまたはその水和物の製造方法 - Google Patents
レボフロキサシンまたはその水和物の製造方法 Download PDFInfo
- Publication number
- JP5065020B2 JP5065020B2 JP2007522417A JP2007522417A JP5065020B2 JP 5065020 B2 JP5065020 B2 JP 5065020B2 JP 2007522417 A JP2007522417 A JP 2007522417A JP 2007522417 A JP2007522417 A JP 2007522417A JP 5065020 B2 JP5065020 B2 JP 5065020B2
- Authority
- JP
- Japan
- Prior art keywords
- levofloxacin
- mixed solvent
- water
- ethyl acetate
- butanol
- 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
- 229960003376 levofloxacin Drugs 0.000 title claims description 62
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 title claims description 45
- 238000000034 method Methods 0.000 title claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 96
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 59
- 239000012046 mixed solvent Substances 0.000 claims description 58
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 52
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 28
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 28
- SUIQUYDRLGGZOL-RCWTXCDDSA-N levofloxacin hemihydrate Chemical compound O.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 SUIQUYDRLGGZOL-RCWTXCDDSA-N 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 15
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 8
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 8
- WKRSSAPQZDHYRV-VIFPVBQESA-N Ofloxacin impurity e Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCNCC1 WKRSSAPQZDHYRV-VIFPVBQESA-N 0.000 claims description 6
- 150000001204 N-oxides Chemical class 0.000 claims description 5
- QEHPHWRZQAZOTI-PPHPATTJSA-N levofloxacin monohydrate Chemical compound O.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 QEHPHWRZQAZOTI-PPHPATTJSA-N 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012535 impurity Substances 0.000 description 23
- 239000002244 precipitate Substances 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 150000004682 monohydrates Chemical class 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 4
- AAEQXEDPVFIFDK-UHFFFAOYSA-N 3-(4-fluorobenzoyl)-2-(2-methylpropanoyl)-n,3-diphenyloxirane-2-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)C(C)C)OC1(C=1C=CC=CC=1)C(=O)C1=CC=C(F)C=C1 AAEQXEDPVFIFDK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- CFLBIADORGSMCX-UHFFFAOYSA-N 2h-1,4-benzoxazine-6-carboxylic acid Chemical compound O1CC=NC2=CC(C(=O)O)=CC=C21 CFLBIADORGSMCX-UHFFFAOYSA-N 0.000 description 1
- -1 4-methyl-1-piperazinyl Chemical group 0.000 description 1
- DCINPPZTEPFLEP-LEMICQRHSA-M C[C@@H](CO)N(C=C(C([O-])=O)C(C1=CC(F)=C2C3N(C)CCNC3)=O)C1=C2[N+]([O-])=O.[K+] Chemical compound C[C@@H](CO)N(C=C(C([O-])=O)C(C1=CC(F)=C2C3N(C)CCNC3)=O)C1=C2[N+]([O-])=O.[K+] DCINPPZTEPFLEP-LEMICQRHSA-M 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020040056637A KR100704641B1 (ko) | 2004-07-21 | 2004-07-21 | 고순도의 레보플록사신 제조방법 |
| KR10-2004-0056637 | 2004-07-21 | ||
| PCT/KR2005/002294 WO2006009374A1 (fr) | 2004-07-21 | 2005-07-18 | Procede pour la preparation de levofloxacine ou de son hydrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008507507A JP2008507507A (ja) | 2008-03-13 |
| JP5065020B2 true JP5065020B2 (ja) | 2012-10-31 |
Family
ID=35785447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007522417A Expired - Fee Related JP5065020B2 (ja) | 2004-07-21 | 2005-07-18 | レボフロキサシンまたはその水和物の製造方法 |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP5065020B2 (fr) |
| KR (1) | KR100704641B1 (fr) |
| CA (1) | CA2573129C (fr) |
| WO (1) | WO2006009374A1 (fr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003028665A2 (fr) | 2001-10-03 | 2003-04-10 | Teva Pharmaceutical Industries Ltd. | Techniques de purification de la lévofloxacine |
| US7964723B2 (en) | 2008-08-02 | 2011-06-21 | Apeloa-Kangyu | And practical process for exclusively producing (S)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido-[1,2,3,de][1,4]benzoxazine-6-carboxylic acid hemihydrate |
| CN111855840A (zh) * | 2020-06-30 | 2020-10-30 | 辰欣药业股份有限公司 | 一种盐酸左氧氟沙星注射液中有关物质的检测方法 |
| CN116953096A (zh) * | 2022-12-24 | 2023-10-27 | 华夏生生药业(北京)有限公司 | 一种左氧氟沙星注射液杂质检测方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4777253A (en) * | 1986-04-25 | 1988-10-11 | Abbott Laboratories | Process for preparation of racemate and optically active ofloxacin and related derivatives |
| JP3105572B2 (ja) * | 1990-03-01 | 2000-11-06 | 第一製薬株式会社 | 水和物の選択的製法 |
| TW208013B (fr) * | 1990-03-01 | 1993-06-21 | Daiichi Co Ltd | |
| KR100309871B1 (ko) * | 1999-02-24 | 2001-10-29 | 윤종용 | (-)피리도벤즈옥사진 카르복실산 유도체의 제조방법 |
| AU2002365416A1 (en) * | 2001-11-29 | 2003-06-10 | Teva Pharmaceutical Industries Ltd. | Methods for the purification of levofloxacin |
| JP2004099494A (ja) * | 2002-09-09 | 2004-04-02 | Shiono Chemical Co Ltd | 光学活性三環式化合物の製造方法 |
| CN1735620A (zh) * | 2002-12-16 | 2006-02-15 | 兰贝克赛实验室有限公司 | 纯的左氧氟沙星半水合物和它的制备方法 |
-
2004
- 2004-07-21 KR KR1020040056637A patent/KR100704641B1/ko active IP Right Grant
-
2005
- 2005-07-18 WO PCT/KR2005/002294 patent/WO2006009374A1/fr active Application Filing
- 2005-07-18 CA CA2573129A patent/CA2573129C/fr not_active Expired - Fee Related
- 2005-07-18 JP JP2007522417A patent/JP5065020B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2008507507A (ja) | 2008-03-13 |
| CA2573129A1 (fr) | 2006-01-26 |
| CA2573129C (fr) | 2012-10-16 |
| WO2006009374A1 (fr) | 2006-01-26 |
| KR20060009155A (ko) | 2006-01-31 |
| KR100704641B1 (ko) | 2007-04-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008516005A (ja) | レトロゾールの改良された調製方法 | |
| JP7368636B2 (ja) | ロキサデュスタット及びその中間体の合成方法とその中間体 | |
| JP5065020B2 (ja) | レボフロキサシンまたはその水和物の製造方法 | |
| JP2021050228A (ja) | ２−アセチル−４Ｈ，９Ｈ−ナフト［２，３−ｂ］フラン−４，９−ジオンの製造方法 | |
| JP7144873B2 (ja) | スガマデクスナトリウム塩の製造方法 | |
| JP5017101B2 (ja) | 不斉四置換炭素原子含有化合物の製法 | |
| JP5757665B2 (ja) | イマチニブ塩基を調製する新規な方法 | |
| JP6831496B2 (ja) | ベンゾオキサゾール誘導体の結晶 | |
| JP2012020970A (ja) | ｛２−アミノ−１，４−ジヒドロ−６−メチル−４−（３−ニトロフェニル）−３，５−ピリジンジカルボン酸３−（１−ジフェニルメチルアゼチジン−３−イル）エステル５−イソプロピルエステル｝の製造方法 | |
| JP3884063B2 (ja) | セフカペンピボキシルのメタンスルホン酸塩 | |
| TW201815779A (zh) | （ｒ）－５－（３，４－二氟苯基）－５－〔（３－甲基－２－氧代吡啶－１（２ｈ）－基）甲基〕咪唑啶－２，４－二酮之製造方法及用於該製造之中間體 | |
| KR960008243B1 (ko) | 헤테로사이클릭 화합물 | |
| WO2006022488A1 (fr) | Procede de purification de cilostazol | |
| CN107365299B (zh) | 一种达比加群酯的制备方法及其中间体 | |
| CN107652269A (zh) | 甲磺酸氟马替尼中间体纯化方法 | |
| JP5279449B2 (ja) | ５−｛４−［２−（５−エチル−２−ピリジル）エトキシ］ベンジル｝−２，４−チアゾリジンジオン塩酸塩の製造方法 | |
| JP2018016569A (ja) | （１ｓ）−１−［３−（ジメチルアミノ）プロピル］−１−（４−フルオロフェニル）−１，３−ジヒドロイソベンゾフラン−５−カルボニトリル蓚酸塩の製造方法 | |
| JP2002371060A (ja) | 光学活性アミノピペリジン誘導体の製造方法 | |
| Bagherpoor et al. | An Efficient Procedure for Development of Levofloxain Hemihydrates Synthesis and Purification | |
| WO2023100110A1 (fr) | Procédé de préparation de brivaracétam | |
| JP2006111561A (ja) | 抗菌薬の１／２水和物の製造方法 | |
| KR20060125218A (ko) | 광학활성 벤족사진 유도체의 제조방법 | |
| JP2022502511A (ja) | アピキサバンの製造方法 | |
| EP3943482A1 (fr) | Procédé de préparation de latanoprostene bunod et de son intermédiaire et compositions les comprenant | |
| JP3953225B2 (ja) | キノリン誘導体の製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080421 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110927 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111226 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20120305 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120605 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120702 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120731 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120809 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5065020 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150817 Year of fee payment: 3 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |