CN113603635B - 一种芳香族二元羧酸酯水解脱羧的方法 - Google Patents

一种芳香族二元羧酸酯水解脱羧的方法 Download PDF

Info

Publication number
CN113603635B
CN113603635B CN202111168246.6A CN202111168246A CN113603635B CN 113603635 B CN113603635 B CN 113603635B CN 202111168246 A CN202111168246 A CN 202111168246A CN 113603635 B CN113603635 B CN 113603635B
Authority
CN
China
Prior art keywords
pressure
reaction
aromatic dicarboxylic
decarboxylation
dicarboxylic acid
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
Application number
CN202111168246.6A
Other languages
English (en)
Other versions
CN113603635A (zh
Inventor
刘鹏
王宇
杨湖平
刘家明
冯生维
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hunan Subo Biotechnology Co ltd
Original Assignee
Hunan Subo Biotechnology Co ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hunan Subo Biotechnology Co ltd filed Critical Hunan Subo Biotechnology Co ltd
Priority to CN202111168246.6A priority Critical patent/CN113603635B/zh
Publication of CN113603635A publication Critical patent/CN113603635A/zh
Application granted granted Critical
Publication of CN113603635B publication Critical patent/CN113603635B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
    • C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
    • C07D251/20—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with no nitrogen atoms directly attached to a ring carbon atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

本发明公开了一种芳香族二元羧酸酯水解脱羧的方法。该方法将芳香族二元羧酸酯、酸性催化剂、水和醇类溶剂加入带有自动泄压装置的高压反应釜中，在恒定压力下保温脱羧反应3~6h，反应完成后负压回收溶剂，降温析晶，离心烘干得到脱羧产物。本发明采用恒压一锅进行水解脱羧的方法，避免了传统高温水解脱羧带来的物料分解和焦化问题，简化了操作工艺，提升了生产效率，同时减少废盐量，降低了环保处理成本。该水解脱羧方法具有成本低、收率高、工艺操作简单等特点，适合规模化生产。

Description

一种芳香族二元羧酸酯水解脱羧的方法
技术领域
本发明涉及化学合成技术领域，具体地为一种芳香族二元羧酸酯水解脱羧的方法。背景技术
二元羧酸酯的水解脱羧反应是非常重要的化学反应，广泛地应用于化工、生物、医药、食品等领域额。传统水解脱羧工艺多采用热化学脱羧或酸碱催化脱羧，但这些工艺分别存在反应效率低下和严重污染环境等问题。
“丙二酸二乙酯在有机合成中应用”，王永利，刘来杰，河北北方学院学报，第21卷第2期，第15~19页，2005年4月，介绍了通过丙二酸二乙酯在芳香环上引入亚甲基，再利用二乙酯基的吸电效应在亚甲基上引入所需要的基团，最后脱去二乙酯基是一类重要的化学反应，由于其是有效的引入活性基团的方法，被用于合成多种芳香族化合物，应用于医药上具有抗菌、消炎、抗癌等重要生物活性；在农业上可作为杀菌、除草和杀虫剂。
专利WO2006067103A3公开了一种芳香族二元羧酸化合物水解脱羧方法，该脱羧条件苛刻，在180℃酸性条件下水解脱羧，高温状态下盐酸和水在反应体系中的浓度极低，不利于脱羧反应，造成反应时间长达24h以上，反应产品焦化严重，收率只有66%。
专利WO2018114484A1公开了一种芳香族二元羧酸酯水解脱羧方法，采用分步脱羧，先碱性条件下脱去一个羧基，更换溶剂后，再将体系pH调至酸性脱去另外一个羧基，经过改进后反应条件温和，收率有较大提高，但两步脱羧分别采用不同溶剂，中间体需要分离，产生大量含盐废水收率低，操作繁琐，不利于工业化。
“An efficient synthesis of 2-alkylpyridines using an alkylation/double decarboxylation strategy”, Craig Donald et al.,《Tetrahedron Letters》，第53卷，第3853-3856页，2012年05月19日，报道了吡啶二元羧酸酯水解分步脱羧的方法，先碱性条件下脱羧，再酸性条件下脱羧，该法脱羧反应时间长达32h，不利于工业化生产，同时酸碱中和产生大量的无机盐，增大了环保处理压力。
“March高等有机化学”，迈克尔B.史密斯，第421-422页，化学工业出版社，2018年3月，对二元羧酸酯水解脱羧反应历程的阐述，羧酸酯基在酸和水存在下先水解脱去醇转变为羧酸基，因二元羧酸化合物热力学不稳定性，在受热状态下分解为CO2和一元羧酸化合物，该过程较易发生，一元羧酸化合物在酸或碱催化剂的存在下受热再次分解得到CO2和脱羧产物。从二元羧酸酯水解脱羧历程分析，该脱羧过程有水和酸或碱催化剂的参与，脱羧进行时应尽可能避免水和酸或碱催化剂的损失；从化学平衡角度分析，在反应同时移出脱羧产生的醇和CO2能够持续推动脱羧正反应的进行。
为实现从源头上减少三废和提高反应收率的目标，有必要开发一种芳香族二元羧酸酯水解脱羧新方法，克服上述现有技术的缺点。
发明内容
本发明的目的就是针对上述缺陷提供一种芳香族二元羧酸酯水解脱羧方法，设计了使用带自动泄压装置的高压釜作为反应器的恒压一锅脱羧法，可同时满足水解脱羧反应对温度的要求又能减少脱羧必需的水和酸催化剂的损失，自动泄压装置可及时排出脱羧反应不断产生的低沸点的醇和CO2，进一步推动脱羧反应的进行和保障反应体系的安全，避免传统高温反应，减少焦化现象，提高了脱羧反应收率，具体方法如下：
将芳香族二元羧酸酯、酸性催化剂、水和醇类溶剂加入带有自动泄压装置的高压反应釜中，密闭搅拌溶解，并将自动泄压装置的压力设置至一定的压力数值；将反应温度升至100~150℃，当釜内压力超过设定压力，泄压阀自动发生泄气，反应体系始终保持在设定压力下保温反应3~6h，取样进行液相色谱分析，当原料≤0.5%，停止反应；降温至70~80℃，反应液负压回收部分溶剂后降温至20~25℃，产物析出，离心过滤，产物烘干。
所述溶剂为异丁醇、正丁醇、仲丁醇、叔丁醇中的一种，其中优选正丁醇。
所述催化剂酸为硫酸、盐酸、硝酸、对甲苯磺酸、甲基磺酸、三氟甲基磺酸中的一种，其中优选硫酸。
催化剂的用量为芳香族二元羧酸酯质量的0.5~5.0%，其中优选1.5~5.0%。
所述自动泄压压力为0.1~0.5MPa，其中优选0.1~0.3 MPa。
所述脱羧温度为100~150℃，其中优选110~120℃。
所述的负压回收溶剂的体积为反应液体积的25~75%，其中优选40~60%。
所述芳香族二元羧酸酯为2-(2-环丙基-2-氧乙基)-2-(吡啶-2-基)丙二酸酯、2-肉桂基-2-(嘧啶-4-基)丙二酸二乙酯、2-烯丙基-2-(1,3,5-三嗪-2-基)丙二酸二乙酯、3-氯-5-三氟甲基-2-吡啶基乙基(二乙基酯)-2-三氟甲基苯甲酰胺中的任意一种。
本发明提供的芳香族二元羧酸酯水解脱羧方法的有益效果：
1、本发明改变了传统高温水解脱羧带来的物料分解和焦化问题，提高了热敏性化合物的水解脱羧收率；
2、改分步水解脱羧为恒压一锅法水解脱羧，简化了操作工艺，缩短了反应时间，提升了生产效率，同时废盐量的减少降低了环保处理成本；
3、水解脱羧产物在醇和水混合反应溶剂中结晶产物纯度高；
4、操作简单，易于工业化。
具体实施方式
下面将结合具体的实施例对本发明进一步说明，当然，以下描述的实施例仅是本发明的一部分，而不是全部的实施例。
<实施例1>
Figure 262015DEST_PATH_IMAGE001
1000ml带有温度计、自动泄压装置的高压反应釜中加入96.0g(0.3mol)2-(2-环丙基-2-氧乙基)-2-(吡啶-2-基)丙二酸酯、400g正丁醇、300g水和1.5g 98%的浓硫酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.1MPa，釜温升至112~113℃，保温反应6h，取样口取样，液相色谱分析原料≤0.5%，降温至70~80℃，负压回收溶剂，回收180g溶剂，再降温至20~25℃，离心过滤，固体烘干得到51.0g 96.0%1-环丙基-3-(吡啶-2-基)丙烷-1-酮，收率93.2%（液相色谱外标法）。
<实施例2>
Figure 52117DEST_PATH_IMAGE001
1000ml带有温度计、自动泄压装置的高压反应釜中加入96.0g(0.3mol)2-(2-环丙基-2-氧乙基)-2-(吡啶-2-基)丙二酸酯、500g正丁醇、100g水和3.0g 99%的甲基磺酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.5MPa，釜温升至116~118℃，保温反应3h，取样口取样，液相色谱分析原料≤0.5%，降温至70~80℃，负压回收溶剂，回收390g溶剂，再降温至20~25℃，离心过滤，固体烘干得到49.5g 96.0%1-环丙基-3-(吡啶-2-基)丙烷-1-酮，收率90.5%（液相色谱外标法）。
<实施例3>
Figure 356846DEST_PATH_IMAGE002
1000ml带有温度计、自动泄压装置的高压反应釜中加入106.3g(0.3mol) 2-肉桂基-2-(嘧啶-4-基)丙二酸二乙酯、450g异丁醇、180g水和3.5g 99%的对甲苯磺酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.2MPa，釜温升至114~115℃，保温反应4h，取样口取样，液相色谱分析原料≤0.5%，降温至70~80℃，负压回收溶剂，回收380g溶剂，再降温至20~25℃，离心过滤，固体烘干得到63.1g 95.9% 4-(4-苯基-3-烯-1-基)嘧啶，收率96.2%（液相色谱外标法）。
<实施例4>
Figure 890595DEST_PATH_IMAGE002
1000ml带有温度计、自动泄压装置的高压反应釜中加入106.3g(0.3mol) 2-肉桂基-2-(嘧啶-4-基)丙二酸二乙酯、630g异丁醇、250g水和2.0g98%的浓硫酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.3MPa，釜温升至146~148℃，保温反应5h，取样口取样，液相色谱跟踪原料≤0.5%，降温至70~80℃，负压回收溶剂，回收420g溶剂，再降温至20~25℃，离心过滤，固体烘干得到60.2g 95.9% 4-(4-苯基-3-烯-1-基)嘧啶，收率91.5%（液相色谱外标法）。
<实施例5>
Figure 227030DEST_PATH_IMAGE003
1000ml带有温度计、自动泄压装置的高压反应釜中加入83.7g(0.3mol) 2-烯丙基-2-(1,3,5-三嗪-2-基)丙二酸二乙酯、500g仲丁醇、250g水和1.5g99%甲基磺酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.4MPa，釜温升至127~128℃，保温反应4h，取样口取样，液相色谱跟踪原料≤0.5%，降温至70~80℃，负压回收溶剂，回收300g溶剂，再降温至20~25℃，离心过滤，固体烘干得到39.5g 96.1% 2-(3-丁烯-1-基)-1,3,5-三嗪，收率93.6%（液相色谱外标法）。
<实施例6>
Figure 453612DEST_PATH_IMAGE003
1000ml带有温度计、自动泄压装置的高压反应釜中加入83.7g(0.3mol) 2-烯丙基-2-(1,3,5-三嗪-2-基)丙二酸二乙酯、350g仲丁醇、200g水和3.0g99%三氟甲基磺酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.3MPa，釜温升至132~133℃，保温反应6h，取样口取样，液相色谱分析原料≤0.5%，降温至70~80℃，负压回收溶剂，回收250g溶剂，再降温至20~25℃，离心过滤，固体烘干得到37.4g 95.9% 2-(3-丁烯-1-基)-1,3,5-三嗪，收率88.6%（液相色谱外标法）。
<实施例7>
Figure 757554DEST_PATH_IMAGE004
1000ml带有温度计、自动泄压装置的高压反应釜中加入108.2g(0.2mol) 3-氯-5-三氟甲基2-吡啶基乙基(二乙基酯)2-三氟甲基苯甲酰胺、450g叔丁醇、200g水和1.8g99%三氟甲基磺酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.4MPa，釜温升至126~127℃，保温反应4h，取样口取样，液相色谱分析原料≤0.5%，降温至70~80℃，负压回收溶剂，回收280g溶剂，再降温至20~25℃，离心过滤，固体烘干得到78.2g 96.0% N-[2-[3-氯-5-(三氟甲基)-2-吡啶]乙基]-2-(三氟甲基)苯甲酰胺，收率94.8%（液相色谱外标法）。
<实施例8>
Figure 845727DEST_PATH_IMAGE004
1000ml带有温度计、自动泄压装置的高压反应釜中加入108.2g(0.2mol) 3-氯-5-三氟甲基2-吡啶基乙基(二乙基酯)2-三氟甲基苯甲酰胺、650g叔丁醇、300g水和3.0g68%浓硝酸后，密闭搅拌溶解，设定自动泄压阀的压力值为0.5MPa，釜温升至100~102℃，保温反应6h，取样口取样，液相色谱分析原料≤0.5%，降温至70~80℃，负压回收溶剂，回收340g溶剂，再降温至20~25℃，离心过滤，固体烘干得到75.0g 95.0% N-[2-[3-氯-5-(三氟甲基)-2-吡啶]乙基]-2-(三氟甲基)苯甲酰胺，收率89.5%（液相色谱外标法）。
以上所述仅是本发明的优选实施方式，本发明的保护范围并不仅局限于上述实施例。凡属于本发明思路下的技术方案均属于本发明的保护范围。应该指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下的改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (7)

1.一种芳香族二元羧酸酯水解脱羧的方法，其特征在于：将2-(2-环丙基-2-氧乙基)-2-(吡啶-2-基)丙二酸酯、2-肉桂基-2-(嘧啶-4-基)丙二酸二乙酯、2-烯丙基-2-(1,3,5-三嗪-2-基)丙二酸二乙酯、3-氯-5-三氟甲基-2-吡啶基乙基(二乙基酯)-2-三氟甲基苯甲酰胺中的任意一种、酸性催化剂、水和醇类溶剂加入到带有自动泄压装置的高压反应釜中，密闭后搅拌溶解，并将自动泄压装置的压力设置至一定的压力数值升温反应，当釜内压力超过设定压力，泄压阀自动排气，使反应体系始终保持在恒定压力下保温反应3~6h，取样进行液相色谱分析，当原料≤0.5%，停止反应；降温至70~80℃，反应液负压回收部分溶剂后降温至20~25℃，产物析出，离心过滤，产物烘干，酸性催化剂的用量为芳香族二元羧酸酯重量的0.5~5.0%，反应式：
Figure 557217DEST_PATH_IMAGE001
。
2.根据权利要求1所述的一种芳香族二元羧酸酯水解脱羧的方法，其特征在于所述醇类溶剂为异丁醇、正丁醇、仲丁醇、叔丁醇中的一种，其用量为芳香族二元羧酸酯质量的4~6倍。
3.根据权利要求1所述的一种芳香族二元羧酸酯水解脱羧的方法，其特征在于水的用量为芳香族二元羧酸酯质量的1~3倍。
4.根据权利要求1所述的一种芳香族二元羧酸酯水解脱羧的方法，其特征在于所述酸性催化剂为硫酸、盐酸、硝酸、对甲苯磺酸、甲基磺酸、三氟甲基磺酸中的一种。
5.根据权利要求1所述的一种芳香族二元羧酸酯水解脱羧的方法，其特征在于所述自动泄压装置的压力设置为0.1~0.5MPa。
6.根据权利要求1所述的一种芳香族二元羧酸酯水解脱羧的方法，其特征在于所述脱羧温度为100~150℃。
7.根据权利要求1所述的一种芳香族二元羧酸酯水解脱羧的方法，其特征在于所述的负压回收溶剂的体积为反应液体积量的25~75%。
CN202111168246.6A 2021-10-08 2021-10-08 一种芳香族二元羧酸酯水解脱羧的方法 Active CN113603635B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111168246.6A CN113603635B (zh) 2021-10-08 2021-10-08 一种芳香族二元羧酸酯水解脱羧的方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111168246.6A CN113603635B (zh) 2021-10-08 2021-10-08 一种芳香族二元羧酸酯水解脱羧的方法

Publications (2)

Publication Number Publication Date
CN113603635A CN113603635A (zh) 2021-11-05
CN113603635B true CN113603635B (zh) 2021-12-24

Family

ID=78343345

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111168246.6A Active CN113603635B (zh) 2021-10-08 2021-10-08 一种芳香族二元羧酸酯水解脱羧的方法

Country Status (1)

Country Link
CN (1) CN113603635B (zh)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1150152A (zh) * 1995-10-10 1997-05-21 弗·哈夫曼-拉罗切有限公司 咪唑并苯并二氮杂草衍生物的制备方法
WO2013034048A1 (en) * 2011-09-08 2013-03-14 Merck Sharp & Dohme Corp. Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases
CN108822024A (zh) * 2018-08-28 2018-11-16 陕西恒润化学工业有限公司 一种氟吡菌酰胺及其合成方法
WO2018215668A1 (en) * 2017-05-26 2018-11-29 Glenmark Pharmaceuticals S.A. Novel inhibitors of map4k1

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1150152A (zh) * 1995-10-10 1997-05-21 弗·哈夫曼-拉罗切有限公司 咪唑并苯并二氮杂草衍生物的制备方法
WO2013034048A1 (en) * 2011-09-08 2013-03-14 Merck Sharp & Dohme Corp. Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases
WO2018215668A1 (en) * 2017-05-26 2018-11-29 Glenmark Pharmaceuticals S.A. Novel inhibitors of map4k1
CN108822024A (zh) * 2018-08-28 2018-11-16 陕西恒润化学工业有限公司 一种氟吡菌酰胺及其合成方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
An efficient synthesis of 2-alkylpyridines using an alkylation/double decarboxylation strategy;Craig Donald et al.;《Tetrahedron Letters》;20120519;第53卷;第3853-3856页 *

Also Published As

Publication number Publication date
CN113603635A (zh) 2021-11-05

Similar Documents

Publication Publication Date Title
CN108017578B (zh) 一种2-氯-n,n-二甲基烟酰胺的制备方法
CN111320572B (zh) 一种取代吡啶的制备方法
CN106278964B (zh) 氟苯尼考的制备方法
CN113603635B (zh) 一种芳香族二元羧酸酯水解脱羧的方法
CN109503513B (zh) 一种非布司他中间体的“一锅法”合成方法
CN107522614B (zh) 一种低碳卤代烷烃用于分离与提纯混合二元酸中戊二酸的方法
CN108585335B (zh) 一种盐酸苯肼生产废液处理及资源回收方法
CN110143916B (zh) 一种氟啶胺的合成工艺
CN102731357A (zh) 高纯度n,n′-二环己基硫脲的制备方法
CN117447427A (zh) 一种呋塞米的制备方法
CN111099975A (zh) 一种5-溴-2-氯-4’-乙氧基二苯甲酮的制备方法
CN103880717B (zh) 二（3-烯丙基-4-羟基苯基）砜及其衍生物的制备方法
CN111393382A (zh) 一种1-乙酸四氮唑的制备方法
CN112125829A (zh) 降低杂质1，3-二甲基脲含量的高纯度灭多威生产方法
CN112142607A (zh) 一种合成间二乙氨基苯酚的方法
CN112961118A (zh) 一种非布司他脱羧杂质的合成方法
CN109928951B (zh) 2-异丙基硫杂蒽酮的制备方法
CN109320472B (zh) 一种3,4-二氯5-氰基异噻唑的制备方法
CN114685300A (zh) 一种邻氯苯甘氨酸的制备方法
CN105254611A (zh) 苯并噻吩-2-羧酸的制备方法
US4337355A (en) Process for preparing 4-hydroxyphenylacetic acid
CN110105362B (zh) 一种杂多酸催化的安全绿色的叶酸合成方法
CN110903252B (zh) 一种4,6-二羟基嘧啶的制备方法
CN115181033B (zh) 一种敌稗催化合成方法
CN108069897B (zh) 一种利用二氧化碳合成烟酸的方法

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
GR01 Patent grant
GR01 Patent grant