CN110256322B - 一种合成阿维巴坦关键中间体及其重结晶工艺 - Google Patents
一种合成阿维巴坦关键中间体及其重结晶工艺 Download PDFInfo
- Publication number
- CN110256322B CN110256322B CN201910567267.1A CN201910567267A CN110256322B CN 110256322 B CN110256322 B CN 110256322B CN 201910567267 A CN201910567267 A CN 201910567267A CN 110256322 B CN110256322 B CN 110256322B
- Authority
- CN
- China
- Prior art keywords
- pyroglutamic acid
- tert
- temperature
- reaction
- butoxycarbonyl
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- NDCUAPJVLWFHHB-UHNVWZDZSA-N avibactam Chemical compound C1N2[C@H](C(N)=O)CC[C@@]1([H])N(OS(O)(=O)=O)C2=O NDCUAPJVLWFHHB-UHNVWZDZSA-N 0.000 title claims abstract description 10
- 229960002379 avibactam Drugs 0.000 title claims abstract description 10
- 238000001953 recrystallisation Methods 0.000 title claims abstract description 9
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 31
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 17
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 12
- 239000000706 filtrate Substances 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 9
- 229940073608 benzyl chloride Drugs 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 238000004042 decolorization Methods 0.000 claims 1
- 229940043131 pyroglutamate Drugs 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 description 15
- 238000010438 heat treatment Methods 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 9
- 238000005303 weighing Methods 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000003781 beta lactamase inhibitor Substances 0.000 description 2
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 238000010583 slow cooling Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 2
- LVFGWOQWXQLVRO-XJDKXYGGSA-N (6r,7r)-7-[[(2e)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;[(2s,5r)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl] hydrogen sulfate Chemical compound NC(=O)[C@@H]1CC[C@H]2N(OS(O)(=O)=O)C(=O)N1C2.S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)/C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 LVFGWOQWXQLVRO-XJDKXYGGSA-N 0.000 description 1
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 1
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229950008167 abamectin Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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 to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D207/28—2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
Description
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910567267.1A CN110256322B (zh) | 2019-06-27 | 2019-06-27 | 一种合成阿维巴坦关键中间体及其重结晶工艺 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910567267.1A CN110256322B (zh) | 2019-06-27 | 2019-06-27 | 一种合成阿维巴坦关键中间体及其重结晶工艺 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110256322A CN110256322A (zh) | 2019-09-20 |
CN110256322B true CN110256322B (zh) | 2023-12-15 |
Family
ID=67922265
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910567267.1A Active CN110256322B (zh) | 2019-06-27 | 2019-06-27 | 一种合成阿维巴坦关键中间体及其重结晶工艺 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110256322B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102812167A (zh) * | 2009-12-30 | 2012-12-05 | 阿维拉制药公司 | 蛋白的配体-介导的共价修饰 |
CN109721522A (zh) * | 2018-12-29 | 2019-05-07 | 常州吉恩药业有限公司 | 一种高品质n-叔丁氧羰基-l-焦谷氨酸苄酯工业化生产方法 |
-
2019
- 2019-06-27 CN CN201910567267.1A patent/CN110256322B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102812167A (zh) * | 2009-12-30 | 2012-12-05 | 阿维拉制药公司 | 蛋白的配体-介导的共价修饰 |
CN109721522A (zh) * | 2018-12-29 | 2019-05-07 | 常州吉恩药业有限公司 | 一种高品质n-叔丁氧羰基-l-焦谷氨酸苄酯工业化生产方法 |
Non-Patent Citations (8)
Title |
---|
A Concise Asymmetric Route to the Bridged Bicyclic Tropane Alkaloid Ferruginine Using Enyne Ring-Closing Metathesis;Varinder K. Aggarwal et al.;《Organic Letters》;第6卷(第9期);第1469-1471页,Supporting Information第S2页 * |
A New Class of Non‑C2‑Symmetric Ligands for Oxidative and Redox-Neutral Palladium-Catalyzed Asymmetric Allylic Alkylations of 1,3-Diketones;Barry M. Trost et al.;《JACS》;第137卷;第2776−2784页 * |
Hetero-Diels–Alder and pyroglutamate approaches to (2S,4R)-2-methylamino-5-hydroxy-4-methylpentanoic acid;James E. Tarver, Jr. et al.;《Tetrahedron》;第60卷;第10277–10284页 * |
Synthesis and evaluation of novel orally active p53–MDM2 interaction inhibitors;Masaki Miyazaki et al.;《Bioorganic & Medicinal Chemistry》;第21卷;第4319-4331页 * |
Synthetic approaches to peptides containing the L-Gln- L -Val-D(S)-Dmt motif;Ghadeer A. R. Y. Suaifan et al.;《Bioorganic & Medicinal Chemistry》;第15卷;第3474–3488页 * |
一锅法合成阿维巴坦关键原料;秦志忠 等;《化学与生物工程》;第39卷(第5期);第32-35页 * |
阿维巴坦关键中间体的合成及结晶工艺;崔召新;《中国优秀硕士学位论文全文数据库 工程科技I辑》;第B016-910页 * |
龙小菊 等.《有机化学实验》.天津科学技术出版社,2018,(第2018年6月第1版),第56-57页. * |
Also Published As
Publication number | Publication date |
---|---|
CN110256322A (zh) | 2019-09-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2839344B2 (ja) | 環状アミノ酸、並びにその中間体の製造方法 | |
CN110590635A (zh) | 左乙拉西坦及其中间体的制备方法 | |
CN110590746A (zh) | 一种低杂质富马酸沃诺拉赞的制备方法 | |
CN101407488B (zh) | 焦谷氨酸醇及其中间体的化学合成方法 | |
CN113024554B (zh) | 一种卢美哌隆中间体的制备方法 | |
CN110256322B (zh) | 一种合成阿维巴坦关键中间体及其重结晶工艺 | |
CN105017229B (zh) | 一种制备咯菌腈的方法 | |
CN106699604B (zh) | 一种沙库比曲及其中间体的制备方法 | |
Szakonyi et al. | Regio-and stereoselective synthesis of the enantiomers of monoterpene-based β-amino acid derivatives | |
CN104130262A (zh) | 一种厄他培南、厄他培南侧链及其制备方法 | |
CN111533746A (zh) | 一种枸橼酸托法替布的合成方法 | |
CN114835654B (zh) | 帕拉米韦关键中间体的制备方法 | |
CN110563699A (zh) | 一种氟呐普拉赞中间体的后处理纯化方法 | |
CN112384493B (zh) | 稠合三环γ-氨基酸衍生物的制备方法及中间体 | |
CN110627637B (zh) | 一步法制备消旋酮异亮氨酸钙 | |
CN111233835A (zh) | 5-(2-氟苯基)-1-(吡啶-3-基磺酰基)-1h-吡咯-3-甲醛制备纯化方法 | |
CN117304194B (zh) | 一种乌帕替尼的合成方法 | |
CN111393412A (zh) | 一种达比加群酯粗品的精制方法 | |
CN102863370A (zh) | 一种抗癫痫药左乙拉西坦的新合成方法 | |
CN116396330B (zh) | 一种环丙基取代的2h-苯并吡喃衍生物的制备方法 | |
CN111440154B (zh) | 一种替格列汀二聚体杂质的合成方法 | |
CN115197178B (zh) | 一种布立西坦关键中间体的合成方法 | |
CN108864090B (zh) | 一种阿哌沙班n-1晶体的制备方法 | |
CN108689914A (zh) | 一种采用中间体制备手性化合物的方法 | |
CN111960984B (zh) | 一种合成多尼培南侧链中间体的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB03 | Change of inventor or designer information | ||
CB03 | Change of inventor or designer information |
Inventor after: Sun Xu Inventor after: Gao Lingfeng Inventor after: Zheng Gengxiu Inventor after: Cui Zhaoxin Inventor after: Zhu Chenxi Inventor after: Peng Benwei Inventor before: Gao Lingfeng Inventor before: Zheng Gengxiu Inventor before: Cui Zhaoxin Inventor before: Zhu Chenxi Inventor before: Sun Xu Inventor before: Peng Benwei |
|
GR01 | Patent grant | ||
GR01 | Patent grant |