CN102070503B - 一种制备吡咯衍生物的方法 - Google Patents
一种制备吡咯衍生物的方法 Download PDFInfo
- Publication number
- CN102070503B CN102070503B CN201010588316A CN201010588316A CN102070503B CN 102070503 B CN102070503 B CN 102070503B CN 201010588316 A CN201010588316 A CN 201010588316A CN 201010588316 A CN201010588316 A CN 201010588316A CN 102070503 B CN102070503 B CN 102070503B
- Authority
- CN
- China
- Prior art keywords
- pyrrole derivative
- formula
- aryl
- pyridine
- alpha
- 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.)
- Expired - Fee Related
Links
- 150000003233 pyrroles Chemical class 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims abstract 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 7
- 238000000605 extraction Methods 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 2
- 125000005002 aryl methyl group Chemical group 0.000 claims 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 238000010992 reflux Methods 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 2
- -1 alkyl glyoxylate Chemical compound 0.000 abstract 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical class BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical compound CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical class CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 238000006086 Paal-Knorr synthesis reaction Methods 0.000 description 2
- 150000008062 acetophenones Chemical class 0.000 description 2
- FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 229940002661 lipitor Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 1
- ADCYRBXQAJXJTD-UHFFFAOYSA-N 1-(4-chlorophenyl)propan-1-one Chemical class CCC(=O)C1=CC=C(Cl)C=C1 ADCYRBXQAJXJTD-UHFFFAOYSA-N 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960001770 atorvastatin calcium Drugs 0.000 description 1
- 150000007980 azole derivatives Chemical class 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000003845 household chemical Substances 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种吡咯衍生物的制备方法。它是以伯胺、乙醛酸烷基酯和α-溴代苯乙酮衍生物为原料,在吡啶存在下,在有机溶剂中回流反应6~12小时,经简易后处理纯化过程即可获得吡咯衍生物。本发明反应条件温和,工艺简单,操作便捷;所得吡咯衍生物有潜在的良好的生物活性,并可以作为有机合成中间体使用。
Description
技术领域
本发明涉及一种吡咯衍生物的制备方法。
背景技术
吡咯类衍生物是一种具有重要生物活性的生物碱,可以作为精细化工产品的重要中间体,在医药、食品、农药、日用化学品、涂料、纺织、印染、造纸、感光材料、高分子材料等领域有着广泛的用途,参考文献见Synlett 1999,1523;Chem.Soc.Rev.1997,26,247。最为显著的例子是世界最畅销药物之一的立普妥(阿托伐他汀钙片或Lipitor),具有降血脂良效,该药物的母核骨架就是吡咯。
特别是当吡咯环上有四个取代基时,它就具有抗菌、抗滤过性病源体、抗痉挛、抗氧化等药效,参考文献见J.Pharm.Sci.1972,61,1908;Pharmazie 1990,45,441;Il Farmaco 1997,52,667;Eur.J.Med.Chem.1999,34,991;Drugs 2000,11,351;Chem.Pharm.Bull.2001,49,1406;Tetrahedron Lett.2003,44,4443。通过Paal-Knorr合成能生成这种类型的吡咯化合物,其中当伯胺参与反应时所生成的是N上含有取代基的吡咯化合物(参考文献见J.Org.Chem.1999,64,2657;Bioorg.Med.Chem.Lett 1999,9,3143;J.Chem.Soc.,Perkin.Trans.1 2000,3389;Org.Lett,2001,3,1201;Synthesis 2001,2003;Org.Lett.2001,3,3297;J.Med.Chem.2002,45,5458)。但由于这类环化合成的反应条件要求比较高,Minetto等提出了通过微波辐射促进Paal-Knorr反应的新方法,制备得到了1,2,3,5-四取代的吡咯衍生物,其中3位是酯基取代基,参考文献见Org.Lett,2004,3,389。
由于1,2,3,5-四取代吡咯衍生物的通常拥有较高的生物活性,而且经常能作为有机合成的重要中间体,因此进一步开发吡咯衍生物的高效的制备方法,对新药筛选有重要意义。
发明内容
本发明的目的是提供一种反应温和、操作简便的制备吡咯衍生物的方法。
吡咯衍生物的制备方法,其步骤是:以伯胺、乙醛酸烷基酯和α-溴代苯乙酮衍生物为原料,在吡啶存在下,在有机溶剂中回流反应6~12小时,经过水洗和萃取、浓缩、柱层析或重结晶纯化过程得到吡咯衍生物;伯胺、乙醛酸烷基酯、α-溴代苯乙酮衍生物和吡啶之间的摩尔比为1∶1∶2~2.2∶4~6;
反应式为:
式中:R1选自C3~C8的烃基、苄基、芳基或取代的芳基;R2选自C1~C4的烃基;R3选自芳基或取代的芳基;所述取代的芳基上的取代基是H、卤素、C1~C4的烃基或C1~C4的烃氧基。
所说的有机溶剂为乙腈或二氯乙烷。
本发明与已有的合成方法相比,具有以下优点:
1)反应条件温和;
2)反应通用性强;
3)投料和后处理都非常简单。
4)反应起始原料容易获得。
具体实施方式
以下实施例将有助于理解本发明,但不限于本发明的内容:
实施例1
把对甲氧基苯胺(10毫摩尔)和乙醛酸乙酯(10毫摩尔)充分搅拌混合之后,加入乙腈(20毫升)、α-溴代苯乙酮(20毫摩尔)、吡啶(50毫摩尔),加热回流反应12小时,反应完毕,经过水洗、二氯乙烷萃取、有机相减压浓缩至干,浓缩的混合物通过重结晶纯化,获得白色的1-(4-甲氧基苯基)-2-苯甲酰基-3-甲酸乙酯-5-苯基吡咯,产率64%;产物物理数据为m.p.136-137℃;IR(neat)v 1689,1649,1507,1470,1235,1082,1030,929,833,738,696cm-1;1H NMR(400MHz,CDCl3)δ7.84(d,J=7.6Hz,2H),7.53(t,J=7.2Hz,1H),7.41(t,J=7.6Hz,2H),7.22-7.20(m,3H),7.15-7.13(m,2H),7.05(d,J=8.4Hz,2H),6.90(s,1H),6.72(d,J=8.0Hz,2H),3.95(q,J=7.2Hz,2H),3.73(s,3H),0.88(t,J=7.2Hz,3H)ppm;13C NMR(100MHz,CDCl3)δ189.51,163.84,159.13,138.62,137.20,135.69,133.18,131.19,129.32,129.09,128.55,128.37,128.16,127.35,117.91,113.93,110.18,60.11,55.23,13.55ppm;MS(ESI):m/z([M+Na]+):448;HRMS(EI):m/z calcd for(C27H23NO4):425.1627;found:425.1626.
实施例2
把对甲基苯胺(10毫摩尔)和乙醛酸乙酯(10毫摩尔)充分搅拌混合之后,加入二氯乙烷(20毫升)、α-溴代苯乙酮(20毫摩尔)、吡啶(40毫摩尔),加热回流反应6小时,反应完毕,经过水洗、二氯乙烷萃取、有机相减压浓缩至干,浓缩的混合物通过重结晶纯化,获得白色的1-(4-甲基苯基)-2-苯甲酰基-3-甲酸乙酯-5-苯基吡咯,产率60%;产物物理数据为m.p.125-126℃;IR(neat)v 1707,1667,1547,1512,1381,1078,1022,927,821,757,690cm-1;1H NMR(400MHz,CDCl3)δ7.77(d,J=7.2Hz,2H),7.47-7.45(m,1H),7.33(t,J=7.6Hz,2H),7.14-7.11(m,3H),7.07-7.04(m,2H),6.93(s,4H),6.83(s,1H),3.86(q,J=7.2Hz,2H),2.18(s,3H),0.79(t,J=7.2Hz,3H)ppm;13C NMR(100MHz,CDCl3)δ189.47,163.85,138.65,138.31,137.08,134.85,133.16,131.20,129.49,128.55,128.12,127.66,127.35,118.06),110.34,60.12,21.09,13.54ppm;MS(ESI):m/z([M+Na]+):432;HRMS(EI):m/z calcd for(C27H23NO3):409.1678;found:409.1685.
实施例3
把苄胺(10毫摩尔)和乙醛酸乙酯(10毫摩尔)充分搅拌混合之后,加入乙腈(20毫升)、α-溴代苯乙酮(22毫摩尔)、吡啶(50毫摩尔),加热回流反应12小时,反应完毕,经过水洗、二氯乙烷萃取、有机相减压浓缩至干,浓缩的混合物通过柱层析纯化,获得浅黄色的1-苄基-2-苯甲酰基-3-甲酸乙酯-5-苯基吡咯产率70%;产物物理数据为IR(neat)v 2980,1707,1644,1452,1248,1210,1175,1075,1029,922,761,725,695cm-1;1H NMR(400MHz,CDCl3)δ7.56(d,J=8.0Hz,2H),7.37-7.31(m,6H),7.23-7.17(m,2H),6.93-6.98(m,3H),6.71-6.69(m,2H),6.65(s,1H),5.29(s,2H),3.68(q,J=7.2Hz,2H),0.70(t,J=6.8Hz,3H)ppm;13C NMR(100MHz,CDCl3)δ189.34,164.14,139.10,137.50,132.99,132.55,131.32,129.60,129.11,128.67,128.51,128.30,127.99,127.35,126.52,120.89,110.85,60.21,48.96,13.44ppm;MS(ESI):m/z([M+Na]+):432;HRMS(EI):m/z calcd for(C27H23NO3):409.1678;found:409.1674.
实施例4
把对甲氧基苯胺(10毫摩尔)和乙醛酸乙酯(10毫摩尔)充分搅拌混合之后,加入乙腈(20毫升)、α-溴代(4-氯苯基)乙酮(21毫摩尔)、吡啶(50毫摩尔),加热回流反应10小时,反应完毕,经过水洗、二氯乙烷萃取、有机相减压浓缩至干,浓缩的混合物通过重结晶纯化,获得浅黄色的1-(4-甲氧基苯基)-2-(4-氯苯基)甲酰基-3-甲酸乙酯-5-(4-氯苯基)吡咯,产率55%;产物物理数据为m.p.170-171℃;IR(neat)v 1706,1662,1583,1471,1425,1396,1224,1080,1011,923,834,778,758,738,688cm-1;1H NMR(400MHz,CDCl3)δ7.78(d,J=8.0Hz,2),7.40(d,J=8.0Hz,2),7.20(d,J=8.0Hz,2H),7.05(dd,J=11.2,8.4Hz,4H),6.90(s,1H),6.75(d,J=8.4Hz,2H),4.02(q,J=7.2Hz,2H),3.76(s,3H),0.97(t,J=7.2Hz,3H)ppm;13C NMR(100MHz,CDCl3)δ188.20,163.54,159.40,139.48,136.85,136.12,135.57,133.53,130.65,129.70,129.56,129.03,128.80,128.50,117.97,114.17,110.41,60.31,55.31,13.73ppm;MS(ESI):m/z([M+Na]+):516;HRMS(EI):m/z calcd for(C27H21Cl2NO4):493.0848;found:493.0847.
Claims (2)
1.一种式(IV)所示的吡咯衍生物的制备方法,其步骤是:以式(I)所示的伯胺、式(II)所示的乙醛酸烃基酯和式(III)所示的α-溴代芳乙酮衍生物为原料,在吡啶存在下,在有机溶剂中回流反应6~12小时,经过水洗和萃取、浓缩、柱层析或重结晶纯化过程得到吡咯衍生物;伯胺、乙醛酸烃基酯、α-溴代芳乙酮衍生物和吡啶之间的摩尔比为1∶1∶2~2.2∶4~6;
反应式为:
式中:R1选自苄基、芳基或取代的芳基;R2选自C1~C4的烃基;R3选自芳基或取代的芳基;所述取代的芳基上的取代基是卤素、C1~C4的烃基或C1~C4的烃氧基。
2.根据权利要求1所述的吡咯衍生物的制备方法,其特征在于所述的有机溶剂为乙腈或二氯乙烷。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201010588316A CN102070503B (zh) | 2010-12-07 | 2010-12-07 | 一种制备吡咯衍生物的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201010588316A CN102070503B (zh) | 2010-12-07 | 2010-12-07 | 一种制备吡咯衍生物的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102070503A CN102070503A (zh) | 2011-05-25 |
CN102070503B true CN102070503B (zh) | 2012-10-17 |
Family
ID=44029284
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201010588316A Expired - Fee Related CN102070503B (zh) | 2010-12-07 | 2010-12-07 | 一种制备吡咯衍生物的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102070503B (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102276601B (zh) * | 2011-06-07 | 2012-10-17 | 浙江大学 | 一种制备中氮茚衍生物的方法 |
CN103408481B (zh) * | 2013-08-30 | 2016-01-20 | 齐齐哈尔大学 | 微波辐射一步合成取代的吡咯-3-甲酸酯化合物的方法 |
CN105017126B (zh) * | 2015-06-17 | 2018-01-19 | 上海麦克林生化科技有限公司 | 全氟烷基吡咯衍生物及其合成方法 |
CN113788777B (zh) * | 2021-09-07 | 2023-04-11 | 华中科技大学 | 一种制备1-取代-3-羰基吡咯的方法 |
-
2010
- 2010-12-07 CN CN201010588316A patent/CN102070503B/zh not_active Expired - Fee Related
Non-Patent Citations (3)
Title |
---|
E. Vedejs, et al..4-Oxazoline Route to Stabilized Azomethine Ylides. Controlled Reduction of Oxazolium Salts.《J.Am.Chem.Soc.》.1988,第110卷(第10期),3238-3246. * |
Giacomo Minetto, et al..Microwave-Assisted Paal-Knorr Reaction. A Rapid Approach to Substituted Pyrroles and Furans.《ORGANIC LETTERS》.2004,第6卷(第3期),389-392. * |
Roland U. Braun, et al..A Novel One-Pot Pyrrole Synthesis via a Coupling-Isomerization-Stetter-Paal-Knorr Sequence.《ORGANIC LETTERS》.2001,第3卷(第21期),3297-3300. * |
Also Published As
Publication number | Publication date |
---|---|
CN102070503A (zh) | 2011-05-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Ramamohan et al. | Simple and highly efficient synthesis of indolo-and pyrrolo [1, 2-a] quinoxalines promoted by molecular iodine | |
Guo et al. | Tailored Synthesis of Skeletally Diverse Stemona Alkaloids through Chemoselective Dyotropic Rearrangements of β‐Lactones | |
CN102070503B (zh) | 一种制备吡咯衍生物的方法 | |
CN103113308B (zh) | 一种制备二氢嘧啶酮衍生物的方法 | |
CN106565742A (zh) | 吲哚酮螺四氢硫代吡喃类衍生物及其制备方法和应用 | |
Vereshchagin et al. | One-pot five-component high diastereoselective synthesis of polysubstituted 2-piperidinones from aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate | |
Chizhova et al. | Acetic anhydride to the rescue: Facile access to privileged 1, 2, 3, 4-tetrahydropyrazino [1, 2-a] indole core via the Castagnoli-Cushman reaction | |
Mondal et al. | Carbene-Catalyzed Direct O-Functionalization of Ketone: Atroposelective Access to Non-C 2-Symmetric Binaphthyls | |
CN103145600A (zh) | 一种银催化的多取代吡咯类化合物的合成方法 | |
CN106866563B (zh) | 一种制备2,4-二取代-1,3,5三嗪衍生物的方法 | |
Terzidis et al. | Chromeno [2, 3-c] pyrroles by one-pot multicomponent domino addition–amination reaction | |
CN107868087B (zh) | 一种制备吡咯并吲哚类衍生物的方法 | |
Yin et al. | Copper-Catalyzed Ring Opening of Furans as a Concise Route to Polysubstituted Furans under Mild Conditions | |
CN102276601B (zh) | 一种制备中氮茚衍生物的方法 | |
CN114605421A (zh) | 螺-2,3-二氢喹啉-4-酮-3,4-二氢香豆素生物活性骨架及其合成方法和应用 | |
CN107879965A (zh) | 一种铑/碳作为催化剂制备吲哚类化合物的方法 | |
CN103435610A (zh) | 一种咪唑并[1,2-a]吡啶类化合物的制备方法 | |
CN114276304A (zh) | 一种含有稠环的医药中间体1,5-苯并二氮杂䓬衍生物的制备方法 | |
CN103467386A (zh) | 芳基嘧啶邻位单氰基化合物及其合成方法 | |
Youssef et al. | Syntheses of new benzoxazole derivatives | |
CN110526850A (zh) | 2,5-二芳基-3-氰基吡咯化合物的制备方法 | |
CN109988090B (zh) | 一种四氢吡咯衍生物及其合成方法和应用 | |
CN109053736A (zh) | 一种吡咯并[1,2-α]吲哚-3-醇衍生物的制备方法 | |
CN106905349A (zh) | 一种含苯并噁唑哌嗪酮类衍生物及其合成方法和应用 | |
CN112745275B (zh) | 1,3,4-恶二唑杂环化合物的合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121017 Termination date: 20151207 |
|
EXPY | Termination of patent right or utility model |