CN101824030B - 一种伊潘立酮的制备方法 - Google Patents
一种伊潘立酮的制备方法 Download PDFInfo
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- CN101824030B CN101824030B CN200910079132.7A CN200910079132A CN101824030B CN 101824030 B CN101824030 B CN 101824030B CN 200910079132 A CN200910079132 A CN 200910079132A CN 101824030 B CN101824030 B CN 101824030B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- XMXHEBAFVSFQEX-UHFFFAOYSA-N iloperidone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 title description 11
- 229960003162 iloperidone Drugs 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims abstract description 19
- -1 1-[4-[3-[4- (6-fluoro-1, 2-benz isoxazole -3-yl)-1-piperidyl] propoxy]-3-methoxyphenyl] ethyl Chemical group 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 14
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 235000015320 potassium carbonate Nutrition 0.000 claims description 8
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 6
- FVHKXXNNJGZOBO-UHFFFAOYSA-N C(C)C(=O)CC.OC1=C(C=CC=C1)OC Chemical compound C(C)C(=O)CC.OC1=C(C=CC=C1)OC FVHKXXNNJGZOBO-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- YUKUDJRCHPSDGC-UHFFFAOYSA-N 1,2-oxazole;hydrochloride Chemical compound Cl.C=1C=NOC=1 YUKUDJRCHPSDGC-UHFFFAOYSA-N 0.000 claims description 5
- 239000012442 inert solvent Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 3
- 208000028017 Psychotic disease Diseases 0.000 abstract 1
- 230000036592 analgesia Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000006227 byproduct Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 3
- 230000000561 anti-psychotic effect Effects 0.000 description 3
- 239000000164 antipsychotic agent Substances 0.000 description 3
- 229940005529 antipsychotics Drugs 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 125000005843 halogen group Chemical group 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
- 238000009413 insulation Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- BGRJTUBHPOOWDU-UHFFFAOYSA-N sulpiride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Abstract
Description
Claims (9)
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CN200910079132.7A CN101824030B (zh) | 2009-03-04 | 2009-03-04 | 一种伊潘立酮的制备方法 |
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CN200910079132.7A CN101824030B (zh) | 2009-03-04 | 2009-03-04 | 一种伊潘立酮的制备方法 |
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CN101824030A CN101824030A (zh) | 2010-09-08 |
CN101824030B true CN101824030B (zh) | 2014-06-18 |
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Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102070626B (zh) * | 2010-12-11 | 2013-02-13 | 海南康虹医药科技开发有限公司 | 一种制备伊潘立酮的新方法 |
CN102643273B (zh) * | 2011-02-18 | 2016-03-02 | 浙江九洲药业股份有限公司 | 一种伊潘立酮的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4366162A (en) * | 1977-11-09 | 1982-12-28 | Ab Ferrosan | Aryl ethers of N-alkyl-piperidines and acid addition salts thereof |
CN1048037A (zh) * | 1989-05-19 | 1990-12-26 | 赫彻斯特-鲁塞尔药物有限公司 | N-(芳氧基烷基)杂芳基呱啶及一杂芳基呱嗪,它们的制备方法以及它们作为药物的应用 |
CN1136275A (zh) * | 1993-10-28 | 1996-11-20 | 赫彻斯特-柔斯尔药物公司 | 芳杂环基哌啶类、吡咯烷类及哌嗪类及其作为抗精神病药和止痛药的用途 |
-
2009
- 2009-03-04 CN CN200910079132.7A patent/CN101824030B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4366162A (en) * | 1977-11-09 | 1982-12-28 | Ab Ferrosan | Aryl ethers of N-alkyl-piperidines and acid addition salts thereof |
CN1048037A (zh) * | 1989-05-19 | 1990-12-26 | 赫彻斯特-鲁塞尔药物有限公司 | N-(芳氧基烷基)杂芳基呱啶及一杂芳基呱嗪,它们的制备方法以及它们作为药物的应用 |
CN1136275A (zh) * | 1993-10-28 | 1996-11-20 | 赫彻斯特-柔斯尔药物公司 | 芳杂环基哌啶类、吡咯烷类及哌嗪类及其作为抗精神病药和止痛药的用途 |
Non-Patent Citations (2)
Title |
---|
3-[ [ (Aryloxy)alkyllpiperidinyl]-l,2-Benzisoxazoleass Dd5-HT2 Antagonists with Potential Atypical Antipsychotic Activity: Antipsychotic Profile of Iloperidone (HP 873);Joseph T. Strupczewski et al.;《J. Med. Chem.》;19951231;第38卷;第1119-1131页 * |
Joseph T. Strupczewski et al..3-[ [ (Aryloxy)alkyllpiperidinyl]-l,2-Benzisoxazoleass Dd5-HT2 Antagonists with Potential Atypical Antipsychotic Activity: Antipsychotic Profile of Iloperidone (HP 873).《J. Med. Chem.》.1995,第38卷第1119-1131页. |
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TR01 | Transfer of patent right |
Effective date of registration: 20210113 Address after: 570314 no.279 Nanhai Avenue, Xiuying District, Haikou City, Hainan Province Patentee after: AVENTIS PHARMA (HAINAN) Co.,Ltd. Address before: 100097, Wanquan mansion, 3 Jin Zhuang, Haidian District, Beijing, Sijiqing Patentee before: BEIJING D-VENTUREPHARM TECHNOLOGY DEVELOPMENT Co.,Ltd. |
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DD01 | Delivery of document by public notice | ||
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Addressee: Song Xuemei Document name: Notice of conformity |
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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 ipyridone Granted publication date: 20140618 Pledgee: Sanya Rural Commercial Bank Co.,Ltd. Pledgor: AVENTIS PHARMA (HAINAN) Co.,Ltd. Registration number: Y2024980014810 |