CN103554031A - 阿齐沙坦中间体的制备方法 - Google Patents
阿齐沙坦中间体的制备方法 Download PDFInfo
- Publication number
- CN103554031A CN103554031A CN201310535874.2A CN201310535874A CN103554031A CN 103554031 A CN103554031 A CN 103554031A CN 201310535874 A CN201310535874 A CN 201310535874A CN 103554031 A CN103554031 A CN 103554031A
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- CN
- China
- Prior art keywords
- solution
- adds
- ethanol
- filter
- azanol
- 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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Links
- 239000005485 Azilsartan Substances 0.000 title claims abstract description 18
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 229960002731 azilsartan Drugs 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 11
- 239000003513 alkali Substances 0.000 claims abstract description 11
- 239000012043 crude product Substances 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 49
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 45
- 239000000243 solution Substances 0.000 claims description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 33
- 239000000047 product Substances 0.000 claims description 27
- 239000002994 raw material Substances 0.000 claims description 12
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical group Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000012065 filter cake Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 7
- 238000007605 air drying Methods 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 5
- 239000008213 purified water Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- 238000007710 freezing Methods 0.000 claims description 3
- 230000008014 freezing Effects 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical group [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 abstract description 17
- 239000012535 impurity Substances 0.000 abstract description 12
- 239000013078 crystal Substances 0.000 abstract 1
- KXPVENIYRMNDKU-UHFFFAOYSA-N ethanol;hydroxylamine Chemical compound ON.CCO KXPVENIYRMNDKU-UHFFFAOYSA-N 0.000 abstract 1
- 230000001376 precipitating effect Effects 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 150000003536 tetrazoles Chemical group 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 2
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical group CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 2
- 229960000932 candesartan Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- PCJFEVUKVKQSSL-UHFFFAOYSA-N 2h-1,2,4-oxadiazol-5-one Chemical group O=C1N=CNO1 PCJFEVUKVKQSSL-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- -1 carboxylate methyl ester Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201310535874.2A CN103554031B (zh) | 2013-11-01 | 2013-11-01 | 阿齐沙坦中间体的制备方法 |
Applications Claiming Priority (1)
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CN201310535874.2A CN103554031B (zh) | 2013-11-01 | 2013-11-01 | 阿齐沙坦中间体的制备方法 |
Publications (2)
Publication Number | Publication Date |
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CN103554031A true CN103554031A (zh) | 2014-02-05 |
CN103554031B CN103554031B (zh) | 2015-04-15 |
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CN201310535874.2A Active CN103554031B (zh) | 2013-11-01 | 2013-11-01 | 阿齐沙坦中间体的制备方法 |
Country Status (1)
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CN (1) | CN103554031B (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103880756A (zh) * | 2014-03-26 | 2014-06-25 | 四川奥邦药业有限公司 | 一种阿齐沙坦中间体的制备方法 |
CN106478515A (zh) * | 2016-10-13 | 2017-03-08 | 艾美科健(中国)生物医药有限公司 | 一种阿齐沙坦中间体的制备方法 |
JP2018002672A (ja) * | 2016-07-05 | 2018-01-11 | 株式会社トクヤマ | アジルサルタンの中間体となるアミドキシム化合物の製造方法、及びアジルサルタンの製造方法 |
WO2018008219A1 (ja) * | 2016-07-05 | 2018-01-11 | 株式会社トクヤマ | アジルサルタン中間体、アジルサルタン、及びこれらの製造方法 |
CN108640911A (zh) * | 2018-04-03 | 2018-10-12 | 山东科兴生物制品有限公司 | 一种阿齐沙坦的新型制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012119573A1 (en) * | 2011-03-04 | 2012-09-13 | Zentiva, K.S. | A method of manufacturing 2-ethoxy-1-((2'-((hydroxyamino) iminomethyl)biphenyl-4- yl)methyl)-1h-benzo [d] imidazole-7-carboxylic acid and its esters |
CN102731491A (zh) * | 2012-07-04 | 2012-10-17 | 北京科莱博医药开发有限责任公司 | 一种阿齐沙坦中间体的制备方法 |
CN102731408A (zh) * | 2012-07-20 | 2012-10-17 | 江苏先声药物研究有限公司 | 一种阿齐沙坦中间体及其制备方法 |
-
2013
- 2013-11-01 CN CN201310535874.2A patent/CN103554031B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012119573A1 (en) * | 2011-03-04 | 2012-09-13 | Zentiva, K.S. | A method of manufacturing 2-ethoxy-1-((2'-((hydroxyamino) iminomethyl)biphenyl-4- yl)methyl)-1h-benzo [d] imidazole-7-carboxylic acid and its esters |
CN102731491A (zh) * | 2012-07-04 | 2012-10-17 | 北京科莱博医药开发有限责任公司 | 一种阿齐沙坦中间体的制备方法 |
CN102731408A (zh) * | 2012-07-20 | 2012-10-17 | 江苏先声药物研究有限公司 | 一种阿齐沙坦中间体及其制备方法 |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103880756A (zh) * | 2014-03-26 | 2014-06-25 | 四川奥邦药业有限公司 | 一种阿齐沙坦中间体的制备方法 |
CN103880756B (zh) * | 2014-03-26 | 2016-06-01 | 四川奥邦药业有限公司 | 一种阿齐沙坦中间体的制备方法 |
JP2018002672A (ja) * | 2016-07-05 | 2018-01-11 | 株式会社トクヤマ | アジルサルタンの中間体となるアミドキシム化合物の製造方法、及びアジルサルタンの製造方法 |
WO2018008219A1 (ja) * | 2016-07-05 | 2018-01-11 | 株式会社トクヤマ | アジルサルタン中間体、アジルサルタン、及びこれらの製造方法 |
CN106478515A (zh) * | 2016-10-13 | 2017-03-08 | 艾美科健(中国)生物医药有限公司 | 一种阿齐沙坦中间体的制备方法 |
CN106478515B (zh) * | 2016-10-13 | 2018-11-23 | 艾美科健(中国)生物医药有限公司 | 一种阿齐沙坦中间体的制备方法 |
CN108640911A (zh) * | 2018-04-03 | 2018-10-12 | 山东科兴生物制品有限公司 | 一种阿齐沙坦的新型制备方法 |
Also Published As
Publication number | Publication date |
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CN103554031B (zh) | 2015-04-15 |
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C06 | Publication | ||
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SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20160325 Address after: 518000 Guangdong city of Shenzhen province Nanshan District Guangdong streets Kexing Science Park B building 4 unit 18 floor area D Patentee after: Shenzhen Measuring Technology Co., Ltd. Address before: 518057 No. 13, science and technology road, Nanshan District Science Park, Guangdong, Shenzhen Patentee before: Shenzhen Kexing Biotech Co., Ltd. |
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C56 | Change in the name or address of the patentee | ||
CP03 | Change of name, title or address |
Address after: 518000 Guangdong city of Shenzhen province Nanshan District Guangdong streets Kexing Science Park B building 4 unit 18 floor area D Patentee after: Shenzhen Xiang Xiang Biotechnology Co., Ltd. Address before: Guangdong city of Shenzhen province Nanshan District Guangdong streets Kexing Science Park B building 4 unit 18 floor area D Patentee before: Shenzhen Measuring Technology Co., Ltd. |
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TR01 | Transfer of patent right |
Effective date of registration: 20180905 Address after: 518000 18, B4 unit, Kexing Science Park, 15 Keyuan Road, Nanshan District, Shenzhen, Guangdong. Patentee after: Shenzhen Kexing Pharmaceutical Co., Ltd. Address before: Guangdong city of Shenzhen province Nanshan District Guangdong streets Kexing Science Park B building 4 unit 18 floor area D Patentee before: Shenzhen Xiang Xiang Biotechnology Co., Ltd. |
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TR01 | Transfer of patent right | ||
CP02 | Change in the address of a patent holder |
Address after: 518000 b1601, Chuangyi technology building, No.1 Keji Road, Maling community, Yuehai street, Nanshan District, Shenzhen City, Guangdong Province Patentee after: SHENZHEN KEXING PHARMACEUTICAL Co.,Ltd. Address before: 518000 18, B4 unit, Kexing Science Park, 15 Keyuan Road, Nanshan District, Shenzhen, Guangdong. Patentee before: SHENZHEN KEXING PHARMACEUTICAL Co.,Ltd. |
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CP02 | Change in the address of a patent holder |