SK286118B6 - Spôsob čistenia lorazepamu - Google Patents
Spôsob čistenia lorazepamu Download PDFInfo
- Publication number
- SK286118B6 SK286118B6 SK1483-2003A SK14832003A SK286118B6 SK 286118 B6 SK286118 B6 SK 286118B6 SK 14832003 A SK14832003 A SK 14832003A SK 286118 B6 SK286118 B6 SK 286118B6
- Authority
- SK
- Slovakia
- Prior art keywords
- lorazepam
- carried out
- process according
- desolvation
- solvate
- Prior art date
Links
- DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 title claims abstract description 65
- 229960004391 lorazepam Drugs 0.000 title claims abstract description 65
- 238000000034 method Methods 0.000 title claims abstract description 30
- 239000012453 solvate Substances 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 5
- 150000002170 ethers Chemical class 0.000 claims abstract description 5
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000002148 esters Chemical class 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 15
- 239000013078 crystal Substances 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 238000004807 desolvation Methods 0.000 claims description 8
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 6
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 6
- -1 aromatic carbonates Chemical class 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- 238000000354 decomposition reaction Methods 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 5
- AZIZBYRGIGKTLW-UHFFFAOYSA-N 1,4-diazepin-2-one Chemical compound O=C1C=NC=CC=N1 AZIZBYRGIGKTLW-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 235000019439 ethyl acetate Nutrition 0.000 claims 2
- 239000003791 organic solvent mixture Substances 0.000 claims 2
- PHMLQARHLDHYFU-UHFFFAOYSA-N oxolane;tetrahydrate Chemical compound O.O.O.O.C1CCOC1 PHMLQARHLDHYFU-UHFFFAOYSA-N 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 abstract description 8
- 239000000047 product Substances 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 150000002576 ketones Chemical class 0.000 abstract description 4
- 239000007884 disintegrant Substances 0.000 abstract 1
- 239000000725 suspension Substances 0.000 description 9
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 239000013557 residual solvent Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 4
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- CYDZMDOLVUBPNL-UHFFFAOYSA-N [7-chloro-5-(2-chlorophenyl)-2-oxo-1,3-dihydro-1,4-benzodiazepin-3-yl] acetate Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(OC(=O)C)N=C1C1=CC=CC=C1Cl CYDZMDOLVUBPNL-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- VUUITUUENPOMIU-UHFFFAOYSA-N 6-chloro-4-(2-chlorophenyl)quinazoline-2-carbaldehyde Chemical compound C12=CC(Cl)=CC=C2N=C(C=O)N=C1C1=CC=CC=C1Cl VUUITUUENPOMIU-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- DIWRORZWFLOCLC-UHFFFAOYSA-N Lorazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-UHFFFAOYSA-N 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 206010034912 Phobia Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
- 229960004535 oxazepam Drugs 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SK1483-2003A SK286118B6 (sk) | 2003-12-03 | 2003-12-03 | Spôsob čistenia lorazepamu |
| CZ20041138A CZ298518B6 (cs) | 2003-12-03 | 2004-11-23 | Zpusob cištení Lorazepamu |
| PCT/SK2004/000015 WO2005054211A1 (en) | 2003-12-03 | 2004-11-30 | A method of purification of lorazepam |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SK1483-2003A SK286118B6 (sk) | 2003-12-03 | 2003-12-03 | Spôsob čistenia lorazepamu |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK14832003A3 SK14832003A3 (sk) | 2005-07-01 |
| SK286118B6 true SK286118B6 (sk) | 2008-04-07 |
Family
ID=34651619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1483-2003A SK286118B6 (sk) | 2003-12-03 | 2003-12-03 | Spôsob čistenia lorazepamu |
Country Status (3)
| Country | Link |
|---|---|
| CZ (1) | CZ298518B6 (cs) |
| SK (1) | SK286118B6 (cs) |
| WO (1) | WO2005054211A1 (cs) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110840898B (zh) * | 2019-11-19 | 2022-05-13 | 湖南洞庭药业股份有限公司 | 光稳定化药物组合物及其制备方法和制药用途 |
| CN110776473B (zh) * | 2019-11-19 | 2023-09-15 | 湖南洞庭药业股份有限公司 | 制备劳拉西泮的方法 |
| CN110683994B (zh) * | 2019-11-19 | 2022-10-11 | 湖南洞庭药业股份有限公司 | 劳拉西泮的新晶型及其制备方法和制药用途 |
| CN110804023A (zh) * | 2019-12-09 | 2020-02-18 | 华中药业股份有限公司 | 一种劳拉西泮的纯化方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001245429A1 (en) * | 2000-03-06 | 2001-09-17 | Teva Pharmaqceutical Industries Ltd. | Process for preparing pure crystalline lorazepam |
-
2003
- 2003-12-03 SK SK1483-2003A patent/SK286118B6/sk not_active IP Right Cessation
-
2004
- 2004-11-23 CZ CZ20041138A patent/CZ298518B6/cs not_active IP Right Cessation
- 2004-11-30 WO PCT/SK2004/000015 patent/WO2005054211A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| SK14832003A3 (sk) | 2005-07-01 |
| WO2005054211A8 (en) | 2005-10-13 |
| CZ20041138A3 (cs) | 2006-12-13 |
| CZ298518B6 (cs) | 2007-10-24 |
| WO2005054211A1 (en) | 2005-06-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| TE4A | Change of owner's address |
Owner name: ZENTIVA, A.S., BRATISLAVA, SK Effective date: 20130927 |
|
| PC4A | Assignment and transfer of rights |
Owner name: SANECA PHARMACEUTICALS A. S., HLOHOVEC, SK Free format text: FORMER OWNER: ZENTIVA, A.S., BRATISLAVA, SK Effective date: 20131002 |
|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20131203 |