JP2013536217A5 - - Google Patents
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- Publication number
- JP2013536217A5 JP2013536217A5 JP2013525364A JP2013525364A JP2013536217A5 JP 2013536217 A5 JP2013536217 A5 JP 2013536217A5 JP 2013525364 A JP2013525364 A JP 2013525364A JP 2013525364 A JP2013525364 A JP 2013525364A JP 2013536217 A5 JP2013536217 A5 JP 2013536217A5
- Authority
- JP
- Japan
- Prior art keywords
- acid
- salt
- iii
- methyl
- benzonitrile
- 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.)
- Granted
Links
- 150000003839 salts Chemical class 0.000 claims 41
- DPVNXTIZXZFMRL-UHFFFAOYSA-N 2-(1h-1,2,4-triazol-5-ylmethyl)benzonitrile Chemical compound N#CC1=CC=CC=C1CC1=NC=NN1 DPVNXTIZXZFMRL-UHFFFAOYSA-N 0.000 claims 38
- 238000000034 method Methods 0.000 claims 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 17
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 claims 17
- 229960003881 letrozole Drugs 0.000 claims 17
- 239000002904 solvent Substances 0.000 claims 17
- 239000002253 acid Substances 0.000 claims 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 10
- -1 aliphatic ketones Chemical class 0.000 claims 8
- 239000012535 impurity Substances 0.000 claims 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 5
- 238000002360 preparation method Methods 0.000 claims 5
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 238000000746 purification Methods 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 3
- 150000002576 ketones Chemical class 0.000 claims 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims 3
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 claims 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- 125000001931 aliphatic group Chemical group 0.000 claims 2
- 230000003197 catalytic effect Effects 0.000 claims 2
- 238000002425 crystallisation Methods 0.000 claims 2
- 230000008025 crystallization Effects 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims 2
- 229940006461 iodide ion Drugs 0.000 claims 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- 150000002763 monocarboxylic acids Chemical class 0.000 claims 2
- 235000006408 oxalic acid Nutrition 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- 229940122815 Aromatase inhibitor Drugs 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 1
- 235000011054 acetic acid Nutrition 0.000 claims 1
- 239000003886 aromatase inhibitor Substances 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
- 229940092714 benzenesulfonic acid Drugs 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 239000001530 fumaric acid Substances 0.000 claims 1
- 238000011065 in-situ storage Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 1
- 235000009518 sodium iodide Nutrition 0.000 claims 1
- 239000001384 succinic acid Substances 0.000 claims 1
- 235000011044 succinic acid Nutrition 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- 150000003628 tricarboxylic acids Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2395/MUM/2010 | 2010-08-27 | ||
| IN2395MU2010 | 2010-08-27 | ||
| PCT/GB2011/051611 WO2012025762A2 (en) | 2010-08-27 | 2011-08-26 | Pure intermediate |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013536217A JP2013536217A (ja) | 2013-09-19 |
| JP2013536217A5 true JP2013536217A5 (enExample) | 2014-10-09 |
| JP5958863B2 JP5958863B2 (ja) | 2016-08-02 |
Family
ID=44653355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013525364A Expired - Fee Related JP5958863B2 (ja) | 2010-08-27 | 2011-08-26 | 純粋な中間体 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9150524B2 (enExample) |
| EP (1) | EP2609087A2 (enExample) |
| JP (1) | JP5958863B2 (enExample) |
| CN (1) | CN103298795A (enExample) |
| CA (1) | CA2809086A1 (enExample) |
| NZ (1) | NZ607428A (enExample) |
| WO (1) | WO2012025762A2 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664810B (zh) * | 2013-12-11 | 2016-09-14 | 深圳劲创生物技术有限公司 | 一种合成来曲唑的工艺 |
| CN117924195A (zh) * | 2023-08-23 | 2024-04-26 | 中科帆凯(大连)新材料有限公司 | 一种制备纯的来曲唑中间体的方法 |
| CN117285477A (zh) * | 2023-09-04 | 2023-12-26 | 河南康达制药有限公司 | 一种来曲唑的合成工艺及其装置 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4978672A (en) | 1986-03-07 | 1990-12-18 | Ciba-Geigy Corporation | Alpha-heterocyclc substituted tolunitriles |
| US4749713A (en) | 1986-03-07 | 1988-06-07 | Ciba-Geigy Corporation | Alpha-heterocycle substituted tolunitriles |
| CN1325482C (zh) | 2001-12-11 | 2007-07-11 | 埃默里大学 | 双(氰基苯基)甲基－三唑在预防乳腺癌中的用途 |
| WO2004076409A2 (en) * | 2003-02-06 | 2004-09-10 | Sun Pharmaceutical Industries Limited | Regiospecific process for the preparation of 4-[1- (4-cyanophenyl)-1-(1,2,4-triazol-1-yl)methyl]benzonitrile |
| AU2003282380A1 (en) * | 2003-11-14 | 2004-06-06 | ADIBHATLA, KALI,SATYA, Bhujanga,rao | A method for the separation of the letrozole precursor 4-1-(1,2,4-triazolyl) methyl benzonitrile from its 1,3,4-triazolyl isomer |
| US20050209294A1 (en) | 2004-03-17 | 2005-09-22 | Wadhwa Lalit K | Process for producing 4-(1H-1,2,4-triazol-1-ylmethyl)benzonitrile |
| CN100560573C (zh) * | 2004-09-28 | 2009-11-18 | 北京德众万全医药科技有限公司 | 一种高纯度来曲唑的制备方法 |
| CA2608904A1 (en) * | 2005-07-06 | 2007-09-07 | Sicor Inc. | Improved process for the preparation of letrozole |
| WO2007039912A1 (en) | 2005-10-05 | 2007-04-12 | Usv Limited | A one pot process for the preparation of 4-[1-cyanophenyl)-1-(1,2,4-triazol-1-yl)methyl]benzonitrile |
| WO2007054964A2 (en) | 2005-10-20 | 2007-05-18 | Cadila Healthcare Limited | Process for the preparation of letrozole |
| WO2007090464A1 (en) | 2006-02-08 | 2007-08-16 | Solmag S.P.A. | Process for preparing letrozole |
| US8003804B2 (en) | 2006-03-17 | 2011-08-23 | Cipla Limited | Synthesis of 4-[1-(4-cyano phenyl)-(1,2,4-triazol-1-yl)methyl] benzonitrile and 4-[1-(1H-1,2,4-triazol-1-yl)methylene benzonitrile intermediate |
| WO2007144896A1 (en) | 2006-06-13 | 2007-12-21 | Natco Pharma Limited | A method of manufacture of letrozole |
| CN101033214B (zh) * | 2006-07-06 | 2011-05-18 | 上海复旦复华药业有限公司 | 来曲唑的制备方法 |
| US8198460B2 (en) | 2007-11-28 | 2012-06-12 | Fresenius Kabi Oncology Ltd. | Process for preparation of letrozole and its intermediates |
| WO2010146391A1 (en) | 2009-06-15 | 2010-12-23 | Generics [Uk] Limited | Regioselective synthesis of letrozole |
| WO2011000396A1 (en) | 2009-07-02 | 2011-01-06 | Synthon B.V. | Purification of letrozole intermediate |
-
2011
- 2011-08-26 WO PCT/GB2011/051611 patent/WO2012025762A2/en not_active Ceased
- 2011-08-26 CN CN2011800500261A patent/CN103298795A/zh active Pending
- 2011-08-26 NZ NZ607428A patent/NZ607428A/en not_active IP Right Cessation
- 2011-08-26 US US13/818,815 patent/US9150524B2/en active Active
- 2011-08-26 CA CA2809086A patent/CA2809086A1/en not_active Abandoned
- 2011-08-26 JP JP2013525364A patent/JP5958863B2/ja not_active Expired - Fee Related
- 2011-08-26 EP EP11757922.7A patent/EP2609087A2/en not_active Withdrawn
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