CN101723955B - Method for preparing olanzapine - Google Patents
Method for preparing olanzapine Download PDFInfo
- Publication number
- CN101723955B CN101723955B CN2008101725718A CN200810172571A CN101723955B CN 101723955 B CN101723955 B CN 101723955B CN 2008101725718 A CN2008101725718 A CN 2008101725718A CN 200810172571 A CN200810172571 A CN 200810172571A CN 101723955 B CN101723955 B CN 101723955B
- Authority
- CN
- China
- Prior art keywords
- amino
- thiotolene
- cyanic acid
- organic solvent
- olanzapine
- 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
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 229960005017 olanzapine Drugs 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims abstract description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 235000019270 ammonium chloride Nutrition 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 235000005074 zinc chloride Nutrition 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 2
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000008878 coupling Effects 0.000 abstract description 3
- 238000010168 coupling process Methods 0.000 abstract description 3
- 238000005859 coupling reaction Methods 0.000 abstract description 3
- 239000007858 starting material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000012046 mixed solvent Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZKNARUVAUOSLGV-UHFFFAOYSA-N N1N=CC=CC=C1.C1=CC=CC=C1 Chemical compound N1N=CC=CC=C1.C1=CC=CC=C1 ZKNARUVAUOSLGV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical group Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 239000011968 lewis acid catalyst Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RSEACRIWQRAVPE-UHFFFAOYSA-N Cc1cc(C#N)c(Nc(cccc2)c2N)[s]1 Chemical compound Cc1cc(C#N)c(Nc(cccc2)c2N)[s]1 RSEACRIWQRAVPE-UHFFFAOYSA-N 0.000 description 1
- NPXUFPFFHANGDL-UHFFFAOYSA-N Cc1cc(C#N)c(Nc(cccc2)c2[N+]([O-])=O)[s]1 Chemical compound Cc1cc(C#N)c(Nc(cccc2)c2[N+]([O-])=O)[s]1 NPXUFPFFHANGDL-UHFFFAOYSA-N 0.000 description 1
- YEHIIKLKSBNZDR-UHFFFAOYSA-N Cl.N1N=CC=CC=C1.C1=CC=CC=C1 Chemical compound Cl.N1N=CC=CC=C1.C1=CC=CC=C1 YEHIIKLKSBNZDR-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 229940039925 zyprexa Drugs 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (8)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008101725718A CN101723955B (en) | 2008-10-30 | 2008-10-30 | Method for preparing olanzapine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008101725718A CN101723955B (en) | 2008-10-30 | 2008-10-30 | Method for preparing olanzapine |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101723955A CN101723955A (en) | 2010-06-09 |
CN101723955B true CN101723955B (en) | 2012-05-30 |
Family
ID=42445573
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2008101725718A Active CN101723955B (en) | 2008-10-30 | 2008-10-30 | Method for preparing olanzapine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101723955B (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102225941B (en) * | 2011-06-01 | 2013-11-27 | 宁波人健医药化工有限公司 | Preparation method of antipsychotic drug olanzapine |
CN102250116B (en) * | 2011-07-12 | 2013-11-27 | 江西富祥药业股份有限公司 | Preparation method of olanzapine |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1150948A (en) * | 1995-11-20 | 1997-06-04 | 沈阳药科大学 | Preparation method of 6,7-dimethoxy-2,4-(1H,3H)-quinazoline diketon |
-
2008
- 2008-10-30 CN CN2008101725718A patent/CN101723955B/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1150948A (en) * | 1995-11-20 | 1997-06-04 | 沈阳药科大学 | Preparation method of 6,7-dimethoxy-2,4-(1H,3H)-quinazoline diketon |
Non-Patent Citations (2)
Title |
---|
方频等.奥氮平合成新工艺研究.《浙江工业大学学报》.2008,第36卷(第1期),16-19. * |
杨先金等.奥氮平的合成工艺改进.《中国新药杂志》.2007,第16卷(第22期),1891-1892. * |
Also Published As
Publication number | Publication date |
---|---|
CN101723955A (en) | 2010-06-09 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method of olanzapine Effective date of registration: 20201226 Granted publication date: 20120530 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISUN PHARMACEUTICAL Co.,Ltd. Registration number: Y2020330001302 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20210425 Granted publication date: 20120530 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISUN PHARMACEUTICAL Co.,Ltd. Registration number: Y2020330001302 |
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PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method of olanzapine Effective date of registration: 20210729 Granted publication date: 20120530 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISUN PHARMACEUTICAL Co.,Ltd. Registration number: Y2021330000982 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230130 Granted publication date: 20120530 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISUN PHARMACEUTICAL Co.,Ltd. Registration number: Y2021330000982 |
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PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method of olanzapine Effective date of registration: 20230228 Granted publication date: 20120530 Pledgee: Industrial Commercial Bank of China Ltd. Taizhou Jiaojiang branch Pledgor: ZHEJIANG HISUN PHARMACEUTICAL Co.,Ltd. Registration number: Y2023330000447 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right |