CN101798289A - 一种埃罗替尼中间体的制备方法 - Google Patents
一种埃罗替尼中间体的制备方法 Download PDFInfo
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- CN101798289A CN101798289A CN201019102004A CN201019102004A CN101798289A CN 101798289 A CN101798289 A CN 101798289A CN 201019102004 A CN201019102004 A CN 201019102004A CN 201019102004 A CN201019102004 A CN 201019102004A CN 101798289 A CN101798289 A CN 101798289A
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- CN
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- Prior art keywords
- methoxy ethoxy
- acid
- erlotinib
- iii
- aminobenzamides
- 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.)
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- 239000005551 L01XE03 - Erlotinib Substances 0.000 title claims abstract description 27
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 229960001433 erlotinib Drugs 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title abstract 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- REPVNSJSTLRQEQ-UHFFFAOYSA-N n,n-dimethylacetamide;n,n-dimethylformamide Chemical compound CN(C)C=O.CN(C)C(C)=O REPVNSJSTLRQEQ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 36
- HTSOCVUNDIHBPV-UHFFFAOYSA-N 2-amino-3-(2-methoxyethoxy)benzamide Chemical class COCCOC=1C(=C(C(=O)N)C=CC1)N HTSOCVUNDIHBPV-UHFFFAOYSA-N 0.000 claims description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 23
- 239000000543 intermediate Substances 0.000 claims description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 10
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 229960001701 chloroform Drugs 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 abstract description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 abstract 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 abstract 2
- 238000007171 acid catalysis Methods 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 230000036571 hydration Effects 0.000 abstract 1
- 238000006703 hydration reaction Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 10
- 238000001816 cooling Methods 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 4
- 229960000935 dehydrated alcohol Drugs 0.000 description 3
- 229960004756 ethanol Drugs 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- -1 2-methoxy ethoxy Chemical group 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
- RJCQBQGAPKAMLL-UHFFFAOYSA-N bromotrifluoromethane Chemical compound FC(F)(F)Br RJCQBQGAPKAMLL-UHFFFAOYSA-N 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201019102004XA CN101798289B (zh) | 2010-02-08 | 2010-02-08 | 一种埃罗替尼中间体的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201019102004XA CN101798289B (zh) | 2010-02-08 | 2010-02-08 | 一种埃罗替尼中间体的制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101798289A true CN101798289A (zh) | 2010-08-11 |
| CN101798289B CN101798289B (zh) | 2012-04-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201019102004XA Active CN101798289B (zh) | 2010-02-08 | 2010-02-08 | 一种埃罗替尼中间体的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101798289B (zh) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321033A (zh) * | 2011-08-22 | 2012-01-18 | 江苏辉丰农化股份有限公司 | 一种它塞瓦的制备方法 |
| CN102584719A (zh) * | 2012-02-02 | 2012-07-18 | 瑞阳制药有限公司 | 盐酸厄洛替尼的制备工艺 |
| CN105646374A (zh) * | 2015-12-31 | 2016-06-08 | 山东罗欣药业集团股份有限公司 | 一种盐酸厄洛替尼的制备方法 |
| CN109206377A (zh) * | 2018-09-19 | 2019-01-15 | 江苏食品药品职业技术学院 | 一种制备n-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺的新方法 |
| CN113603650A (zh) * | 2021-08-03 | 2021-11-05 | 杭州职业技术学院 | 一种埃罗替尼关键中间体的催化环合制备方法及其应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4569876B2 (ja) * | 2003-07-30 | 2010-10-27 | 宇部興産株式会社 | ６，７−ビス（２−メトキシエトキシ）キナゾリン−４−オンの製造法 |
| CN101463013B (zh) * | 2007-12-21 | 2011-06-22 | 上海百灵医药科技有限公司 | 一种盐酸厄洛替尼的制备方法 |
-
2010
- 2010-02-08 CN CN201019102004XA patent/CN101798289B/zh active Active
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321033A (zh) * | 2011-08-22 | 2012-01-18 | 江苏辉丰农化股份有限公司 | 一种它塞瓦的制备方法 |
| CN102321033B (zh) * | 2011-08-22 | 2013-10-09 | 江苏辉丰农化股份有限公司 | 一种它塞瓦的制备方法 |
| CN102584719A (zh) * | 2012-02-02 | 2012-07-18 | 瑞阳制药有限公司 | 盐酸厄洛替尼的制备工艺 |
| CN105646374A (zh) * | 2015-12-31 | 2016-06-08 | 山东罗欣药业集团股份有限公司 | 一种盐酸厄洛替尼的制备方法 |
| CN105646374B (zh) * | 2015-12-31 | 2018-11-27 | 山东罗欣药业集团恒欣药业有限公司 | 一种盐酸厄洛替尼的制备方法 |
| CN109206377A (zh) * | 2018-09-19 | 2019-01-15 | 江苏食品药品职业技术学院 | 一种制备n-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺的新方法 |
| CN109206377B (zh) * | 2018-09-19 | 2021-08-27 | 江苏食品药品职业技术学院 | 一种制备n-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺的新方法 |
| CN113603650A (zh) * | 2021-08-03 | 2021-11-05 | 杭州职业技术学院 | 一种埃罗替尼关键中间体的催化环合制备方法及其应用 |
| CN113603650B (zh) * | 2021-08-03 | 2023-03-10 | 杭州职业技术学院 | 一种埃罗替尼关键中间体的催化环合制备方法及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101798289B (zh) | 2012-04-18 |
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| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Method for preparing Erlotinib intermediate Effective date of registration: 20140320 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000178 |
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Date of cancellation: 20141030 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000178 |
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Denomination of invention: Method for preparing Erlotinib intermediate Effective date of registration: 20141031 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000913 |
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Date of cancellation: 20151021 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Hongqiao branch Pledgor: Tianjin Weijie Technology Co., Ltd. Registration number: 2014990000913 |
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Denomination of invention: Method for preparing Erlotinib intermediate Effective date of registration: 20151021 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2015990000906 |
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Date of cancellation: 20161017 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2015990000906 |
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Denomination of invention: Method for preparing Erlotinib intermediate Effective date of registration: 20161017 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Wei Jie Technology Co., Ltd.|Tianjin Wei Czech Pharmaceutical Co., Ltd. Registration number: 2016990000880 |
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Date of cancellation: 20171018 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2016990000880 |
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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: Method for preparing Erlotinib intermediate Effective date of registration: 20171018 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2017990000966 |
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Date of cancellation: 20181018 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2017990000966 |
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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: Method for preparing Erlotinib intermediate Effective date of registration: 20181018 Granted publication date: 20120418 Pledgee: Bank of Tianjin, Limited by Share Ltd, Tianma subbranch Pledgor: Tianjin Weijie Technology Co., Ltd.|Tianjin Weijie Pharmaceutical Co., Ltd. Registration number: 2018990000977 |
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Change date: 20210930 Registration number: 2018990000977 Pledgee after: Bank of Tianjin Co.,Ltd. second center sub branch Pledgee before: Bank of Tianjin Limited by Share Ltd. Tianma subbranch |