CN102174020B - 合成有机化合物的方法 - Google Patents
合成有机化合物的方法 Download PDFInfo
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- CN102174020B CN102174020B CN2011100581773A CN201110058177A CN102174020B CN 102174020 B CN102174020 B CN 102174020B CN 2011100581773 A CN2011100581773 A CN 2011100581773A CN 201110058177 A CN201110058177 A CN 201110058177A CN 102174020 B CN102174020 B CN 102174020B
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- milliliters
- trifluoromethyl
- imidazoles
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- 238000000034 method Methods 0.000 title claims abstract description 21
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- 239000002904 solvent Substances 0.000 claims description 9
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- 239000003513 alkali Substances 0.000 claims description 6
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- AIDLAEPHWROGFI-UHFFFAOYSA-N 2-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=C(C(O)=O)C=CC=C1C(O)=O AIDLAEPHWROGFI-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 9
- WWTGXYAJVXKEKL-UHFFFAOYSA-N 3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)aniline Chemical compound C1=NC(C)=CN1C1=CC(N)=CC(C(F)(F)F)=C1 WWTGXYAJVXKEKL-UHFFFAOYSA-N 0.000 abstract 1
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- 239000007789 gas Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 150000005226 trifluoromethylbenzenes Chemical class 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/07—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms
- C07C205/11—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings
- C07C205/12—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings the six-membered aromatic ring or a condensed ring system containing that ring being substituted by halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68897605P | 2005-06-09 | 2005-06-09 | |
| US60/688,976 | 2005-06-09 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200680019924XA Division CN101189212B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102174020A CN102174020A (zh) | 2011-09-07 |
| CN102174020B true CN102174020B (zh) | 2012-11-07 |
Family
ID=37149980
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| CN200680019924XA Expired - Fee Related CN101189212B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN2011100572469A Expired - Fee Related CN102174019B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN2011100581769A Pending CN102180796A (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN2011100574125A Expired - Fee Related CN102180836B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN2011100581773A Expired - Fee Related CN102174020B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
Family Applications Before (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100581788A Expired - Fee Related CN102174021B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN200680019924XA Expired - Fee Related CN101189212B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN2011100572469A Expired - Fee Related CN102174019B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN2011100581769A Pending CN102180796A (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
| CN2011100574125A Expired - Fee Related CN102180836B (zh) | 2005-06-09 | 2006-06-07 | 合成有机化合物的方法 |
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| EP (3) | EP2292607B1 (enExample) |
| JP (2) | JP5225078B2 (enExample) |
| KR (2) | KR101249199B1 (enExample) |
| CN (6) | CN102174021B (enExample) |
| AR (1) | AR057056A1 (enExample) |
| AT (1) | ATE540931T1 (enExample) |
| AU (3) | AU2006258050B2 (enExample) |
| BR (1) | BRPI0611683A2 (enExample) |
| CA (4) | CA2942046A1 (enExample) |
| DK (2) | DK2266961T3 (enExample) |
| ES (3) | ES2465522T3 (enExample) |
| GT (1) | GT200600202AA (enExample) |
| HU (1) | HUE028024T2 (enExample) |
| IN (2) | IN2014DN08588A (enExample) |
| JO (1) | JO2758B1 (enExample) |
| MX (1) | MX2007015609A (enExample) |
| MY (1) | MY146795A (enExample) |
| PE (3) | PE20100715A1 (enExample) |
| PL (3) | PL2266961T3 (enExample) |
| PT (3) | PT2292607E (enExample) |
| RU (1) | RU2446162C2 (enExample) |
| SI (2) | SI2266961T1 (enExample) |
| TW (1) | TWI380981B (enExample) |
| WO (1) | WO2006135640A2 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1930136B (zh) | 2004-03-05 | 2012-02-08 | 日产化学工业株式会社 | 异*唑啉取代苯甲酰胺化合物及有害生物防除剂 |
| MY146795A (en) * | 2005-06-09 | 2012-09-28 | Novartis Ag | Process for the synthesis of organic compounds |
| TW200803740A (en) | 2005-12-16 | 2008-01-16 | Du Pont | 5-aryl isoxazolines for controlling invertebrate pests |
| TWI412322B (zh) | 2005-12-30 | 2013-10-21 | Du Pont | 控制無脊椎害蟲之異唑啉 |
| BRPI0809770B8 (pt) | 2007-06-13 | 2022-12-06 | Du Pont | Composto e composição para controlar uma praga de invertebrados |
| TWI430995B (zh) | 2007-06-26 | 2014-03-21 | Du Pont | 萘異唑啉無脊椎有害動物控制劑 |
| DK2957284T3 (en) | 2007-06-27 | 2018-02-05 | Du Pont | PROCEDURE TO CHECK ANIMALS FOR ANIMALS |
| TWI600639B (zh) | 2007-08-17 | 2017-10-01 | 杜邦股份有限公司 | 製備５-鹵烷基-４，５-二氫異唑衍生物之化合物 |
| KR20100075996A (ko) | 2007-10-03 | 2010-07-05 | 이 아이 듀폰 디 네모아 앤드 캄파니 | 무척추 해충의 방제를 위한 나프탈렌 이속사졸린 화합물 |
| TWI583664B (zh) | 2008-04-09 | 2017-05-21 | 杜邦股份有限公司 | 羰基化合物及其製備方法 |
| US20100016590A1 (en) * | 2008-07-17 | 2010-01-21 | Teva Pharmaceutical Industries Ltd. | Nilotinib intermediates and preparation thereof |
| EP2530081A3 (en) | 2008-11-05 | 2013-04-10 | Teva Pharmaceutical Industries, Ltd. | Nilotinib HCI crystalline forms |
| WO2010060074A1 (en) * | 2008-11-24 | 2010-05-27 | Teva Pharmaceutical Industries Ltd. | Preparation of nilotinib and intermediates thereof |
| US20110053968A1 (en) | 2009-06-09 | 2011-03-03 | Auspex Pharmaceuticals, Inc. | Aminopyrimidine inhibitors of tyrosine kinase |
| MX2012013758A (es) | 2010-05-27 | 2013-01-24 | Du Pont | Forma cristalina de 4-[5-[3-cloro-5-trifluorometil)fenil]-4,5-dihi dro-5-(trifluorometil)-3-isoxazolil]-n-[2-oxo-2-[(2,2,2-trifluoro etil)amino]etil]-1-naftalenocarboxamida. |
| BR112014015720B1 (pt) | 2011-12-30 | 2020-03-17 | Hanmi Pharm. Co., Ltd. | Derivados de tieno[3,2-d]pirimidina, composição farmacêutica e uso dos mesmos para a prevenção ou tratamento de uma doença causada por ativação anormal de uma proteína quinase |
| CN102592837B (zh) * | 2012-03-12 | 2014-01-15 | 河北师范大学 | 制备超级电容器用四氯合金属季铵盐掺杂聚苯胺电极的方法 |
| CN103694176B (zh) * | 2014-01-07 | 2015-02-18 | 苏州立新制药有限公司 | 尼洛替尼中间体的制备方法 |
| CN104592122B (zh) * | 2014-12-09 | 2018-01-23 | 凯莱英医药集团（天津）股份有限公司 | 3‑(4‑甲基‑1h‑咪唑‑1‑基)‑5‑(三氟甲基)苯胺的制备方法 |
| CN105985293B (zh) * | 2015-03-04 | 2018-04-03 | 埃斯特维华义制药有限公司 | 尼洛替尼中间体的制备方法 |
| EP3095782A1 (en) | 2015-05-18 | 2016-11-23 | Esteve Química, S.A. | New method for preparing 3-(4-methyl-1h-imidazol-1-yl)-5-(trifluoromethyl)benzenamine |
| CN107201532B (zh) * | 2017-05-09 | 2019-08-27 | 吉林凯莱英医药化学有限公司 | 芳香化合物的硝化方法 |
| WO2019130254A1 (en) * | 2018-01-01 | 2019-07-04 | Laurus Labs Ltd | An improved process for 3-(4-methyl-1h-imidazol-1-yl)-5-(trifluoromethyl) aniline |
| CN108530364B (zh) * | 2018-04-10 | 2020-01-21 | 江苏创诺制药有限公司 | 一种3-(4-甲基-1h-咪唑-1-基)-5-三氟甲基苯胺单盐酸盐的晶型及其应用 |
| EP3806858A4 (en) | 2018-06-15 | 2022-03-09 | Handa Pharmaceuticals, Inc. | KINA INHIBITOR SALTS AND COMPOSITIONS THEREOF |
| US11014945B2 (en) * | 2019-04-06 | 2021-05-25 | Trinapco, Inc. | Sulfonyldiazoles and N-(fluorosulfonyl)azoles, and methods of making the same |
| EP3904342A1 (en) | 2020-04-28 | 2021-11-03 | Grindeks, A Joint Stock Company | Process for the preparation of 3-(trifluoromethyl)-5-(4-methyl-1h-imidazole-1-yl)-benzeneamine hydrochloride |
| CN114751836B (zh) * | 2021-02-23 | 2024-05-31 | 四川青木制药有限公司 | 3-(4-甲基-1h-咪唑-1-基)-5-(三氟甲基)苯胺合成方法及其中间体 |
| CN114853734A (zh) * | 2022-06-14 | 2022-08-05 | 海南鑫开源医药科技有限公司 | 一种尼洛替尼游离碱的制备方法 |
| CN116478319B (zh) * | 2022-11-07 | 2025-07-01 | 华北电力大学 | 一种离子共价有机聚合物的制备方法及其在碱性环境吸附ReO4-的应用 |
| CN115626880B (zh) * | 2022-11-15 | 2023-11-14 | 常州大学 | 3-硝基-5-氰基三氟甲苯的合成方法 |
| CN118108670B (zh) * | 2023-12-28 | 2025-07-01 | 江苏希迪制药有限公司 | 尼罗替尼中间体3-(4-甲基-1h-咪唑-1-基)-5-(三氟甲基)苯胺的精制纯化方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0166533A1 (en) * | 1984-05-29 | 1986-01-02 | Pfizer Limited | Quinolone inotropic agents |
| CN85104392A (zh) * | 1985-01-30 | 1986-12-24 | 辉瑞公司 | 喹诺酮变力剂的制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1051076A1 (ru) * | 1982-04-09 | 1983-10-30 | Алтайский политехнический институт | Способ получени производных имидазола |
| GB8413685D0 (en) * | 1984-05-29 | 1984-07-04 | Pfizer Ltd | Quinolone inotropic agents |
| HN2001000008A (es) * | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
| GB0023383D0 (en) * | 2000-09-23 | 2000-11-08 | Synprotec Ltd | 3,5-Bis (Trifluormethyl)Benzene derivatives |
| PE20040522A1 (es) * | 2002-05-29 | 2004-09-28 | Novartis Ag | Derivados de diarilurea dependientes de la cinasa de proteina |
| GB0215676D0 (en) * | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| GB0222514D0 (en) | 2002-09-27 | 2002-11-06 | Novartis Ag | Organic compounds |
| CN1939910A (zh) * | 2004-12-31 | 2007-04-04 | 孙飘扬 | 氨基嘧啶类化合物及其盐和其制备方法与药物用途 |
| GT200600207A (es) * | 2005-06-09 | 2007-01-15 | Novartis Ag | Proceso para la síntesis de compuestos orgánicos |
| MY146795A (en) * | 2005-06-09 | 2012-09-28 | Novartis Ag | Process for the synthesis of organic compounds |
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- 2010-07-12 US US12/834,295 patent/US8008504B2/en not_active Expired - Fee Related
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0166533A1 (en) * | 1984-05-29 | 1986-01-02 | Pfizer Limited | Quinolone inotropic agents |
| CN85104392A (zh) * | 1985-01-30 | 1986-12-24 | 辉瑞公司 | 喹诺酮变力剂的制备方法 |
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