CN106496130A - 一种甲基酮衍生物及其制备方法与应用 - Google Patents

一种甲基酮衍生物及其制备方法与应用 Download PDF

Info

Publication number
CN106496130A
CN106496130A CN201610813031.8A CN201610813031A CN106496130A CN 106496130 A CN106496130 A CN 106496130A CN 201610813031 A CN201610813031 A CN 201610813031A CN 106496130 A CN106496130 A CN 106496130A
Authority
CN
China
Prior art keywords
ketone
ketone derivatives
phenyl
methyl
preparation
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
Application number
CN201610813031.8A
Other languages
English (en)
Other versions
CN106496130B (zh
Inventor
邹建平
张沛之
李建安
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.)
Suzhou University
Original Assignee
Suzhou University
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 Suzhou University filed Critical Suzhou University
Priority to CN201610813031.8A priority Critical patent/CN106496130B/zh
Publication of CN106496130A publication Critical patent/CN106496130A/zh
Application granted granted Critical
Publication of CN106496130B publication Critical patent/CN106496130B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic 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
    • C07D239/28Heterocyclic 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/34One oxygen atom
    • C07D239/36One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
    • C07D213/62Oxygen or sulfur atoms
    • C07D213/63One oxygen atom
    • C07D213/64One oxygen atom attached in position 2 or 6
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
    • C07D213/62Oxygen or sulfur atoms
    • C07D213/69Two or more oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
    • C07D213/78Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79Acids; Esters
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
    • C07D213/78Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79Acids; Esters
    • C07D213/803Processes of preparation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic 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
    • C07D239/28Heterocyclic 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52Two oxygen atoms
    • C07D239/54Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06Pyrimidine radicals
    • C07H19/073Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明公开了一种甲基酮衍生物及其制备方法与应用,将酮衍生物、有机过氧化物溶于溶剂中,于80‑130℃反应,获得甲基嘧啶酮和甲基吡啶酮衍生物。本发明使用酮衍生物为起始物,原料易得、种类很多;利用本发明的方法得到的产物类型多样,既可以直接使用、又可以用于其他进一步的反应。本发明方法无金属参与,适合于制药工艺。本发明方法路线简短、反应条件温和、反应操作和后处理过程简单、产率较高,适合于规模化生产。

Description

一种甲基酮衍生物及其制备方法与应用
技术领域
本发明属于有机化合物的制备技术领域,具体涉及一种甲基嘧啶酮和甲基吡啶酮衍生物的制备方法及其应用。
背景技术
甲基嘧啶酮衍生物是一类重要的天然产物、药物合成中间体,它们是遗传物质的重要组成部分。5-甲基-2,4(1H,3H)-嘧啶二酮(胸腺嘧啶)是脱氧核糖核酸(DNA)、转移核糖核酸(t-RNA)中的碱基之一,是遗传物质的重要组成部分。此外,5-甲基-2,4(1H,3H)-嘧啶二酮(胸腺嘧啶)可用于合成抗艾滋病药物、抗肿瘤和抗病毒药物zidovudine(齐多夫定,AZT)、stavudine (司他夫定,D4T)及thymidine (Thd);同时AZT也是埃博拉病毒的有效抑制剂,D4T具有抗肺结核病毒的作用,Thd对白血病细胞L1210及人类免疫缺陷病毒CEM具有较好的抑制活性(参见: Ulas Darda Bayraktar, Luis A. Diaz, Brittany Ashlock,Ngoc Toomey, Lisa Cabral, Soley Bayraktar, Denise Pereira, Dirk P. Dittmer,Juan Carlos Ramos, Leukemia & Lymphoma, 2014, 55(4), 786– 794; B. Dhotare, A.Chattopadhyay, Synthesis2001, 1337- 1340; Monika Johar, Tracey Manning,Dennis Y. Kunimotob and Rakesh Kumar, Bioorganic & Medicinal Chemistry 13(2005) 6663–6671; Jan Balzarini, Sofie Celen, Anna Karlsson, Tjibbe de Groot,Alfons Verbruggen and Guy Bormans, Antiviral Chemistry & Chemotherapy, 2006,17, 17–23)。
生物活性实验表明,5-甲基-4-苯氨基嘧啶对Phosphodiesterase 4B (PDE4B)具有选择性抑制作用,具有良好的消炎作用(参见:Tahara, T.; Zhang, Z.; Ohno, M.;Hirao, Y.; Hosaka, N.; Doi, H.; Suzuki, M.; Onoe, H. EJNMMI Research, 2015,5, 2-9)。
吡啶酮衍生物是一类重要的天然生物碱,它存在于许多天然药物中;Eberli等人公开了一种由3-甲基吡啶-2-酮制备过氧化3-甲基吡啶-2-酮的方法,其生物活性实验表明,它在维生素C的存在下可为细胞提供氧气,使细胞在无氧环境下可以存活,其技术路线如下:
现有技术中,5-甲基嘧啶-4-酮衍生物的合成方法主要有以下几种:
Lee等公开了一种5-甲基嘧啶-4-酮的合成方法。该方法需要有机锌试剂,存在反应条件苛刻、底物适用范围窄等不足;其技术路线如下:
Hsu等人公开了一种由苯甲脒盐酸盐和2-甲基乙酰乙酸乙酯反应制备2-苯基-5,6-二甲基嘧啶-4-酮的方法。该方法具有反应条件苛刻、底物适用范围窄等不足(参见: Tice,C. M.; Hsu, A. C. T. Synthesis and Chemistry of Agrochemicals VI, Chapter 5,2009, pp 41–50)。其技术路线如下:
甲基嘧啶酮可以进一步反应合成重要的化合物。比如由5-甲基嘧啶-4-酮-2-硫酮转化成2-苯基-5-甲基嘧啶-4-酮衍生物,其技术路线如下:
现有技术中,3-甲基吡啶-2-酮衍生物的合成方法主要有以下几种:
由甲基乙酰氧基吡啶合成甲基吡啶-2-酮、由己二烯酰基叠氮制备3-甲基吡啶-2-酮、由2-甲氧基-3-甲基吡啶制备3-甲基吡啶酮、从烯胺出发经一系列反应制备3-甲基吡啶-2-酮衍生物、由2-氯-3-甲基吡啶制备3-甲基吡啶-2-酮衍生物。但是现有方法存在底物难以得到、适用范围窄、反应步骤长、产率低、不适合放大的不足。因此寻找一种原料来源简单、符合绿色化学要求、反应条件温和、普适性好的甲基嘧啶酮和甲基吡啶酮衍生物的制备方法很重要。
发明内容
本发明的发明目的是提供一种甲基嘧啶酮和甲基吡啶酮衍生物的制备方法。其具有收率高、反应条件温和、普适性好、无金属参与、环境友好的优点。
为达到上述发明目的,本发明采用的技术方案是:一种甲基酮衍生物的制备方法,包括以下步骤:将酮衍生物、有机过氧化物溶于溶剂中,于80-130℃反应,获得甲基酮衍生物;
所述酮衍生物如下列结构通式所示:
其中X为碳或氮;R1选自氢、C1~C4烷基、羟基或芳基中的一种;R2选自氢、C1~C4烷基、酯基或芳基中的一种;
所述有机过氧化物如下列化学结构通式所示:
其中R3选自氢、叔丁基、苯基异丙基和苯甲酰基中的一种;R4选自氢、叔丁基、苯基异丙基和苯甲酰基中的一种;
所述溶剂选自:乙醇、叔丁醇、乙腈、乙酸、丙酸、甲苯、二甲基甲酰胺中的一种;
所述甲基酮衍生物如下列结构通式所示:
上述技术方案中,所述酮衍生物选自2,6-二苯基嘧啶-4-酮、6-苯基嘧啶-4-酮、2-(4-氟苯基)嘧啶-4-酮、2-(4-氰基苯基)-6-甲基嘧啶-4-酮、2-乙基-6-苯基嘧啶-4-酮、2-羟基-6-苯基嘧啶-4-酮、2-苯基-6-(4-甲苯基)嘧啶-4-酮、2-苯基-6-(4-甲氧苯基)嘧啶-4-酮、4,6-二(4-溴苯基)吡啶-2-酮、4,6-二甲基吡啶-2-酮、4-乙基吡啶-2-酮、4-(4-甲氧基苯基)-6-(4-溴苯基)吡啶-2-酮、4-苯基-6-(4-甲氧基苯基)吡啶-2-酮、4-(4-甲苯基)-6-苯基吡啶-2-酮、6-苯基吡啶-2-酮、4-(4-氯苯基)-6-羟基吡啶-2-酮、4-苯基-6-甲基吡啶-2-酮、6-甲基吡啶-2-酮-4-甲酸丙酯中的一种。
上述技术方案中,利用薄层色谱(TLC)跟踪反应直至完全结束。
上述技术方案中,按摩尔比,酮衍生物∶有机过氧化物为1∶(1~4);
上述技术方案中,反应结束后对产物进行柱层析分离提纯处理。
本发明的反应在空气中进行,避免现有合成步骤反应条件苛刻的问题。
本发明进一步公开了上述甲基酮衍生物的制备方法制备的甲基酮衍生物,包括甲基嘧啶酮和甲基吡啶酮衍生物。
本发明进一步公开了上述甲基酮衍生物在制备药物中的应用;所述药物为抑制剂、消炎药物、抗肿瘤药物或者抗病毒药物。
本发明进一步公开了上述甲基酮衍生物在制备遗传物质中的应用。
上述技术方案的反应过程可表示为:
由于上述技术方案的运用,本发明与现有技术相比具有下列优点:
1.本发明使用酮衍生物为起始物,首次与有机过氧化物在溶剂中反应得到产物甲基酮衍生物,包括甲基嘧啶酮和甲基吡啶酮衍生物;具有原料易得、产物种类很多的优点。
2.本发明公开的甲基酮衍生物制备方法无金属参与,利用本发明的方法得到的产物类型多样,既可以直接使用、又可以用于其他进一步的反应,特别适合于制药工艺,可以由此得到多种有效药物。
3.本发明公开的甲基酮衍生物制备方法步骤简单、反应条件温和、反应操作和后处理过程简单,产率较高,解决了现有技术存在底物难以得到、适用范围窄、反应步骤长、产率低、不适合放大的缺陷;适合于规模生产。
具体实施方式
下面结合实施例对本发明作进一步描述:
本发明的反应在空气中进行。
实施例一:2,6-二苯基-5-甲基嘧啶-4-酮的合成
以2,6-二苯基嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入2,6-二苯基嘧啶-4-酮(0.248 g,1 mmol)、叔丁基过氧化氢(0.09g,1 mmol),和2毫升乙酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 =1:1),得到目标产物(产率63%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ12.85 (s, 1H), 8.17(d, J = 7.1 Hz, 2H), 7.68 (d, J = 6.6 Hz, 2H), 7.63 – 7.46 (m, 6H), 2.10 (s,3H)。
实施例二:5-甲基-6-苯基嘧啶-4-酮的合成
以6-苯基嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入6-苯基嘧啶-4-酮(0.172 g,1 mmol)、叔丁基过氧化氢(0.18 g,2mmol),和2毫升乙酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 =1:1),得到目标产物(产率85%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ12.85 (s, 1H), 8.80(s, 1H), 8.17 (d, J = 7.1 Hz, 2H), 7.63 – 7.46 (m, 3H), 2.14 (s, 3H)。
实施例三:2-(4-氟苯基)-5-甲基嘧啶-4-酮的合成
以2-(4-氟苯基)嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入2-(4-氟苯基)嘧啶-4-酮(0.190 g,1 mmol)、叔丁基过氧化氢(0.27 g,3 mmol),和2毫升乙酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 =1:1),得到目标产物(产率84%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ12.15 (s, 1H), 7.95(s, 1H), 8.15 – 7.99 (m, 2H), 7.44 – 7.30 (m, 2H), 2.35 (s, 3H)。
实施例四:2-(4-氰基苯基)-5,6-二甲基嘧啶-4-酮的合成
以2-(4-氰基苯基)-6-甲基嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入2-(4-氰基苯基)-6-甲基嘧啶-4-酮(0.211 g,1 mmol)、过氧化二异丙苯(1.08 g,4 mmol)和2毫升乙醇,80 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 =1:1),得到目标产物(产率76%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ12.15 (s, 1H), 8.09 –7.89 (m, 2H), 7.63 – 7.45 (m, 2H), 3.50 (s, 3H), 2.35 (s, 3H)。
实施例五:2-乙基-5-甲基-6-苯基嘧啶-4-酮的合成
以2-乙基-6-苯基嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入2-乙基-6-苯基嘧啶-4-酮(0.200 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升乙腈,90 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 =1:1),得到目标产物(产率73%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ12.80 (s, 1H), 8.17(d, J = 7.1 Hz, 2H), 7.63 – 7.46 (m, 3H), 2.63 (q, J = 6.8 Hz, 2H), 2.14 (s,3H), 1.24 (t, J = 6.8 Hz, 3H)。
实施例六:2-羟基-5-甲基-6-苯基嘧啶-4-酮的合成
以2-羟基-6-苯基嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入2-羟基-6-苯基嘧啶-4-酮(0.188 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升甲苯,100 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 =1:1),得到目标产物(产率73%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ12.72 (s, 1H), 11.31(s, 1H), 8.17 (d, J = 7.1 Hz, 2H), 7.63 – 7.46 (m, 3H), 2.24 (s, 3H)。
实施例七:2-苯基-5-甲基-6-(4-甲苯基)嘧啶-4-酮的合成
以2-苯基-6-(4-甲苯基)嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入2-苯基-6-(4-甲苯基)嘧啶-4-酮(0.262 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升甲苯,110 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率96%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ) δ 12.69 (s, 1H), 8.17(d, J = 7.2 Hz, 2H), 7.56 (dd, J = 17.9, 6.9 Hz, 4H), 7.42 (s, 1H), 7.34 (d,J = 7.6 Hz, 2H), 2.50 – 2.35 (s, 3H), 2.14 (s, 3H)。
实施例八:2-苯基-5-甲基-6-(4-甲氧基苯基)嘧啶-4-酮的合成
以2-苯基-6-(4-甲氧基苯基)嘧啶-4-酮作为原料,其反应步骤如下:
在反应管中加入2-苯基-6-(4-甲氧基苯基)嘧啶-4-酮(0.278 g,1 mmol)、叔丁基苯甲酰基过氧化物(0.389 g,2 mmol)和2毫升二甲基甲酰胺,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率84%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ12.77 (s, 1H), 8.10(dd, J = 57.9, 24.6 Hz, 2H), 7.81 – 7.44 (m, 5H), 7.06 (dd, J = 22.3, 8.8 Hz,2H), 3.86 (s, 3H), 2.13 (s, 2H)。
实施例九:4,6-二(4-溴苯基)-3-甲基吡啶-2-酮的合成
以4,6-二(4-溴苯基)吡啶-4-酮作为原料,其反应步骤如下:
在反应管中加入4,6-二(4-溴苯基)吡啶-4-酮(0.402 g,1 mmol)、叔丁基苯甲酰基过氧化物(0.584 g,3 mmol)和2毫升二甲基甲酰胺,130 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率73%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ) : δ11.83 (s, 1H), 7.73– 7.53 (m, 6H), 7.28 – 7.33 (d, 2H), 6.41 (s, 1H), 2.00 (s, 3H)。
实施例十:3,4,6-三甲基吡啶-2-酮的合成
以4,6-二甲基吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入4,6-二甲基吡啶-2-酮(0.123 g,1 mmol)、二叔丁基过氧化物(0.438 g,3 mmol)和2毫升醋酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率63%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ11.89 (s, 1H), 5.71(s, 1H), 2.42 (s, 3H), 2.31 (s, 3H), 2.25 (s, 3H)。
实施例十一:3-甲基-4-乙基吡啶-2-酮的合成
以4-乙基吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入4-乙基吡啶-2-酮(0.123 g,1 mmol)、二叔丁基过氧化物(0.584g,4 mmol)和2毫升丙酸,110 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率65%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ11.29 (s, 1H), 7.43 –7.10 (m, 2H), 2.63 (q, J = 6.8 Hz, 2H), 2.31 (s, 3H), 1.24 (t, J = 6.8 Hz,3H)。
实施例十二: 3-甲基-4-(4-甲氧基苯基)-6-(4-溴苯基)吡啶-2-酮的合成
以4-(4-甲氧基苯基)-6-(4-溴苯基)吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入4-(4-甲氧基苯基)-6-(4-溴苯基)吡啶-2-酮(0.355 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升丙酸,100℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率78%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ) : δ11.79 (s, 1H), 7.73(dd, J = 45.6, 7.2 Hz, 4H), 7.41 (d, J = 7.2 Hz, 2H), 7.07 (d, J = 6.8 Hz,2H), 6.58 (s, 1H), 3.84 (s, 3H), 2.03 (s, 3H)。
实施例十三:3-甲基-4-苯基-6-(4-甲氧基苯基)吡啶-2-酮的合成
以4-苯基-6-(4-甲氧基苯基)吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入4-苯基-6-(4-甲氧基苯基)吡啶-2-酮(0.277 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升醋酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率86%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ) : δ11.77 (s, 1H), 7.78(d, J = 5.9 Hz, 2H), 7.35 – 7.58 (m, 5H), 7.04 (d, J = 5.4 Hz, 2H), 6.44 (s,1H), 3.84 (s, 3H), 1.99 (s, 3H)。
实施例十四:3-甲基-4-(4-甲苯基)-6-苯基吡啶-2-酮的合成
以4-(4-甲苯基)-6-苯基吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入4-(4-甲苯基)-6-苯基吡啶-2-酮(0.261 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升叔丁醇,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率87%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ) : δ 11.86 (s, 1H), 7.81(d, J = 8.0 Hz, 2H), 7.48 (d, J = 7.3 Hz, 2H), 7.37 – 7.29 (m, 5H), 6.49 (s,1H), 2.44 (s, 3H), 1.99 (s, 3H)。
实施例十五:3-甲基-6-苯基吡啶-2-酮的合成
以6-苯基吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入6-苯基吡啶-2-酮(0.171 g,1 mmol)、过氧化二异丙苯(0.81 g,3mmol)和2毫升醋酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率67%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ 11.37 (s, 1H), 7.83–7.70 (m, 2H), 7.60–7.46 (m, 4H), 6.21–6.03 (m, 1H), 2.44 (s, 3H)。
实施例十六:3-甲基-4-(4-氯苯基)-6-羟基吡啶-2-酮的合成
以4-(4-氯苯基)-6-羟基吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入4-(4-氯苯基)-6-羟基吡啶-2-酮(0.221 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升醋酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率88%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ): δ 11.37 (s, 1H), 10.93(s, 1H), 7.53 –7.38 (m, 2H), 7.35 – 7.21 (m, 2H), 6.41 (s, 1H), 2.15 (s, 3H)。
实施例十七:3,6-二甲基-4-苯基吡啶-2-酮的合成
以4-苯基-6-甲基吡啶-2-酮作为原料,其反应步骤如下:
在反应管中加入4-苯基-6-甲基吡啶-2-酮(0.185 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升醋酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率91%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ) : δ11.67 (s, 1H), 7.46(d, J = 7.4 Hz, 2H), 7.41 (s, 1H), 7.33 (d, J = 6.8 Hz, 2H), 5.91 (s, 1H),2.25 (s, 3H), 1.97 (s, 3H)。
实施例十八:3,6-二甲基吡啶-2-酮-4-甲酸丙酯的合成
以6-甲基吡啶-2-酮-4-甲酸丙酯作为原料,其反应步骤如下:
在反应管中加入6-甲基吡啶-2-酮-4-甲酸丙酯(0.195 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升醋酸,120 ℃反应;
TLC跟踪反应直至完全结束;
反应结束后得到的粗产物经柱层析分离(石油醚:乙酸乙酯 = 1:1),得到目标产物(产率71%)。产物的分析数据如下:1H NMR (400 MHz, DMSO-d 6 ) : δ 11.87 (s, 1H), 6.14(s, 1H), 4.23 (d, J = 6.6 Hz, 2H), 2.19 (s, 3H), 2.10 (s, 3H), 1.72 (m, J =14.1, 6.9 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H)。
实施例十九:2-(1-甲基-6-氧代-2,3-二氧杂-5-氮杂双环[2.2.2]辛-7-烯-5-基)乙酸(2-(2-(2-甲氧基乙氧基)乙氧基))乙酯(1)的合成
以3-甲基吡啶-2-酮作为原料,其反应步骤如下:
(1) 化合物19-2的合成步骤:
在反应器中加入吡啶-2-酮19-1(0.095 g,1 mmol)、过氧化二异丙苯(0.81 g,3 mmol)和2毫升醋酸,120 ℃反应,TLC跟踪反应直至完全。反应结束后得到的粗产物经柱层析(石油醚:乙酸乙酯 = 1:1) 分离提纯,得目标产物19-2(产率85%)。产物的分析数据如下:1HNMR (400 MHz, CDCl3):δ 13.07 (s, 1H), 7.38 (dd, J = 9.1, 6.9 Hz, 1H), 6.43(d, J = 9.1 Hz, 1H), 6.09 (d,J= 6.9 Hz, 1H), 2.37 (s, 3H)。
(2) 化合物19-4的合成步骤:
在反应器中加入3-甲基-2-吡啶酮19-2(0.2 g,1.83 mmol),2-溴乙酸-2-[2-(2-甲氧乙氧基)乙氧基]乙酯19-3 (0.78 g, 2.75 mmol),碳酸钾(0.76 g,5.50 mmol)和20毫升DMF,室温下搅拌反应,TLC跟踪至反应结束。反应产物在真空下浓缩,残渣用乙酸乙酯溶解、水洗,有机层用硫酸镁干燥,浓缩,粗产物经柱层析(二氯甲烷:甲醇= 9:1)分离提纯,得到目标产物19-4(产率64%)。产物的分析数据如下:1H NMR (400 MHz, CDCl3): δ 7.21−7.16(m, 1H), 7.11−7.06 (m, 1H), 6.08 (t, J = 6.8 Hz, 1H), 4.63 (s, 2H), 4.34−4.19(m, 2H), 3.72−3.45 (m, 10H), 3.33 (s, 3H), 2.10 (s, 3H)。
(3) 化合物1的合成步骤:
在反应器中加入化合物19-4(0.09 g,0.29 mmol),三苯基膦(0.001 g)和10毫升二氯甲烷,鼓入氧气并剧烈搅拌5分钟,反应体系在氧气氛围下冷却至0℃,然后用高强度的钠灯照射1小时。反应结束后,真空浓缩,粗产物经柱层析(二氯甲烷:甲醇=20:1)分离纯化,得到过氧化物1(产率86%)。产物的分析数据如下:1H NMR (300 MHz, CDCl3): δ 6.96 (dd, J =7.8, 5.3 Hz, 1H), 6.47 (dd, J = 7.8, 1.8 Hz, 1H), 5.74 (dd,J = 5.3, 1.8 Hz,1H), 4.72 (d, J = 18.1 Hz, 1H), 4.41−4.18 (m, 2H), 3.91 (d, J = 18.1 Hz, 1H),3.85−3.48 (m, 10H), 3.39 (s, 3H), 1.63 (s, 3H), 1.57 (s, 3H), 4.20 (m, 2H),3.92 (d, J = 18.1 Hz, 1H), 3.81−3.45 (m, 10H), 3.38 (s, 3H), 1.62 (s, 3H),1.56 (s, 3H)。化合物1在维生素C的存在下可为细胞提供氧气,使细胞在无氧环境下可以存活。
实施例二十:3'-叠氮基-3'-脱氧胸苷AZT(20-5)的合成
以嘧啶-2,4(1H, 3H)-二酮20-1作为原料,其反应步骤如下:
(1) 化合物20-2的合成步骤:
在反应器中加入嘧啶-2,4-二酮20-1(0.112 g,1 mmol)、过氧化二异丙苯(0.81 g,3mmol)和2毫升醋酸,120 ℃下反应,TLC跟踪反应至结束。浓缩后得到的粗产物经柱层析(石油醚:乙酸乙酯 = 1:1) 分离纯化,得到目标产物20-2(产率87%)。产物的分析数据如下:1HNMR (400 MHz, CDCl3):δ11.32 (s, 1H), 11.15 (s, 1H), 7.19 (s, 1H), 2.34 (s,3H)。
(2) 化合物20-4的合成步骤:
在反应器中加入化合物20-2 (0.530 g, 4.2 mmol), 20-3 (0.388 g, 1.4 mmol)和40毫升无水乙腈,氩气保护室温下向溶液中逐滴加入二(三甲基硅)乙酰胺(2.2 mL, 8.7mmol),搅拌3小时后降温至-30℃,向体系中加入三氟甲磺酸三甲基硅酯 (1 mL, 5.6mmol) ,室温下搅拌,TLC跟踪反应至结束。反应产物中加入二氯甲烷,有机层分别用饱和碳酸氢钠溶液、水和饱和食盐水洗涤,干燥,浓缩,柱层析(MeOH:CHCl3=3:100)分离提纯,得到目标产物20-4(产率68%)。产物分析数据如下: 1H NMR (400 MHz, CDCl3):δ8.2 (s, 1H),7.2–8.0 (m, 6H), 6.26 (dd, J = 6.1, 3.2 Hz, 1H), 6.17 (t, J= 6.2 Hz, 1H),4.20-4.71 (m, 4H), 2.21–2.92 (m, 2H), 1.95 (s, 3H)。
(3) 化合物20-5(AZT)的合成步骤:
在反应器中加入化合物20-4 (0.326 g, 0.88 mmol),饱和的氨甲醇溶液30mL,室温下搅拌,TLC跟踪反应至结束。浓缩除去溶剂,柱层析(MeOH:CHCl3=5:100)分离提纯,得到目标产物20-5(产率81%)。产物的分析数据如下:1H NMR (400 MHz, CDCl3):δ 8.53 (s, 1H),7.37 (s, 1H), 6.05 (t, J = 6.4 Hz, 1H), 4.38–4.41 (m, 1H), 4.00–4.04 (m, 1H),3.95–3.98 (m, 1H), 3.81 (dd, J = 11.8, 2.3 Hz, 1H), 2.52 (m, 1H), 2.42 (m,1H), 1.92 (s, 3H)。
化合物20-5为已被批准上市的抗艾滋病药物,商品名为zidovudine(齐多夫定,AZT),同时它也是埃博拉病毒的有效抑制剂。
实施例二十一:3'-脱氧-2',3'-双脱氢胸苷d4T(21-3)的合成
以5-甲基胸腺嘧啶20-2作为原料,其反应步骤如下:
(1) 化合物21-2的合成步骤:
在反应器中加入5-甲基胸腺嘧啶20-2 (0.530 g, 4.2 mmol),化合物21-1 (0.328 g,1.4 mmol)和40毫升无水乙腈,氩气保护室温下向溶液中逐滴加入二(三甲基硅)乙酰胺(2.2 mL, 8.7 mmol),搅拌3小时后降温至-30℃,向体系中加入三氟甲磺酸三甲基硅酯 (1mL, 5.6 mmol) ,室温下搅拌,TLC跟踪反应至结束。反应产物中加入二氯甲烷,有机层分别用饱和碳酸氢钠溶液、水和饱和食盐水洗涤,干燥,浓缩,柱层析(MeOH:CHCl3=3:100)分离提纯,得到目标产物21-2(产率70%)。产物分析数据如下:1H NMR (400 MHz, CDCl3):δ11.31(s, 1H), 8.21 (s, 1H), 7.24–8.01 (m, 5H), 6.53 (d, J = 6.1 Hz, 1H), 5.82-5.74(t, J = 6.2 Hz, 2H), 5.05-4.99 (m, 1H), 4.53 (d, J = 3.2 Hz, 2H), 1.95 (s,3H)。
(3) 化合物21-3(d4T)的合成步骤:
在反应器中加入化合物21-2 (0.288 g, 0.88 mmol),饱和的氨甲醇溶液30mL,室温下搅拌反应,TLC跟踪反应至结束。浓缩除去溶剂,柱层析(MeOH:CHCl3=5:100)分离提纯,得到目标产物21-3(产率75%)。产物分析数据如下:1H NMR (400 MHz, CDCl3):δ 11.31 (s,1H), 8.2 (s, 1H), 6.53 (d, J = 6.1 Hz, 1H), 5.82-5.74 (t, J = 6.2 Hz, 2H),5.54 (s, 1H), 5.05-4.99 (m, 1H), 4.53 (d, J = 3.2 Hz, 2H), 1.95 (s, 3H)。
化合物21-3为已被批准上市的抗艾滋病药物,商品名为stavudine (司他夫定,D4T),同时化合物21-3具有抗肺结核病毒的作用。
实施例二十二:胸苷(22-3,Thd)的合成
以5-甲基胸腺嘧啶20-2作为原料,其反应步骤如下:
(1) 化合物22-2的合成步骤:
在反应器中加入5-甲基胸腺嘧啶20-2 (0.530 g, 4.2 mmol), 化合物22-1 (0.353g, 1.4 mmol)和40毫升无水乙腈,氩气保护室温下向溶液中逐滴加入二(三甲基硅)乙酰胺(2.2 mL, 8.7 mmol),搅拌3小时后降温至-30℃,向体系中加入三氟甲磺酸三甲基硅酯 (1mL, 5.6 mmol) ,室温下搅拌,TLC跟踪反应至结束。反应产物中加入二氯甲烷,有机层分别用饱和碳酸氢钠溶液、水和饱和食盐水洗涤,干燥,浓缩,柱层析(MeOH:CHCl3=3:100)分离提纯,得到目标产物22-2(产率73%)。产物分析数据如下: 1H NMR (400 MHz, CDCl3):δ8.01(d, J = 8.1 Hz, 1H), 7.84 (s, 1H), 8.0–7.23 (m, 5H), 5.73 (d, J = 8.2 Hz,1H), 4.73-5.21 (m, 2H), 3.93 (d, J = 3.1 Hz, 1H), 3.75-3.81 (m, 2H), 3.37 (s,1H), 2.27 (t, J = 3.6 Hz, 2H), 1.90 (s, 3H)。
(3) 化合物22-3(Thd)的合成步骤:
在反应器中加入化合物22-2 (0.288 g, 0.88 mmol),饱和的氨甲醇溶液30mL,室温下搅拌反应,TLC跟踪反应至结束。浓缩除去溶剂,柱层析(MeOH:CHCl3=5:100)分离提纯,得到目标产物22-3(产率78%)。产物分析数据如下:1H NMR (400 MHz, CDCl3):δ8.02 (d, J =8.1 Hz, 1H), 7.88 (s, 1H), 5.70 (d, J = 8.2 Hz, 1H), 4.86-5.20 (m, 2H), 3.95(d, J = 3.1 Hz, 1H), 3.64-3.83 (m, 2H), 3.39 (s, 1H), 2.26 (t, J = 3.6 Hz,2H), 1.91 (s, 3H)。
化合物22-3对白血病细胞L1210及人类免疫缺陷病毒CEM具有较好的抑制活性。

Claims (10)

1.一种甲基酮衍生物的制备方法,其特征在于:包括以下步骤:将酮衍生物、有机过氧化物溶于溶剂中,于80~130℃反应,得到甲基酮衍生物;
所述酮衍生物如下列结构通式所示:
其中X为碳或氮;R1选自氢、C1~C4烷基、羟基或芳基中的一种;R2选自氢、C1~C4烷基、酯基或芳基中的一种;
所述有机过氧化物如下列化学结构通式所示:
其中R3选自氢、叔丁基、苯基异丙基和苯甲酰基中的一种;R4选自氢、叔丁基、苯基异丙基和苯甲酰基中的一种;
所述溶剂选自:乙醇、叔丁醇、乙腈、乙酸、丙酸、甲苯、二甲基甲酰胺中的一种;
所述甲基酮衍生物如下列结构通式所示:
2.根据权利要求1所述甲基酮衍生物的制备方法,其特征在于:按摩尔比,酮衍生物∶有机过氧化物为1∶(1~4)。
3.根据权利要求1所述甲基酮衍生物的制备方法,其特征在于:反应结束后对产物进行柱层析分离提纯处理。
4.根据权利要求1所述甲基酮衍生物的制备方法,其特征在于:所述酮衍生物选自2,6-二苯基嘧啶-4-酮、6-苯基嘧啶-4-酮、2-(4-氟苯基)嘧啶-4-酮、2-(4-氰基苯基)-6-甲基嘧啶-4-酮、2-乙基-6-苯基嘧啶-4-酮、2-羟基-6-苯基嘧啶-4-酮、2-苯基-6-(4-甲苯基)嘧啶-4-酮、2-苯基-6-(4-甲氧苯基)嘧啶-4-酮、4,6-二(4-溴苯基)吡啶-2-酮、4,6-二甲基吡啶-2-酮、4-乙基吡啶-2-酮、4-(4-甲氧基苯基)-6-(4-溴苯基)吡啶-2-酮、4-苯基-6-(4-甲氧基苯基)吡啶-2-酮、4-(4-甲苯基)-6-苯基吡啶-2-酮、6-苯基吡啶-2-酮、4-(4-氯苯基)-6-羟基吡啶-2-酮、4-苯基-6-甲基吡啶-2-酮、6-甲基吡啶-2-酮-4-甲酸丙酯中的一种。
5.根据权利要求1所述甲基酮衍生物的制备方法,其特征在于:利用薄层色谱跟踪反应直至完全结束。
6.根据权利要求1所述甲基酮衍生物的制备方法,其特征在于:反应在空气中进行。
7.根据权利要求1所述甲基酮衍生物的制备方法制备的甲基酮衍生物。
8.权利要求7所述甲基酮衍生物在制备药物中的应用。
9.根据权利要求8所述的应用,其特征在于:所述药物为抑制剂、消炎药物、抗肿瘤药物或者抗病毒药物。
10.权利要求7所述甲基酮衍生物在制备遗传物质中的应用。
CN201610813031.8A 2016-09-09 2016-09-09 一种甲基酮衍生物及其制备方法与应用 Active CN106496130B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610813031.8A CN106496130B (zh) 2016-09-09 2016-09-09 一种甲基酮衍生物及其制备方法与应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610813031.8A CN106496130B (zh) 2016-09-09 2016-09-09 一种甲基酮衍生物及其制备方法与应用

Publications (2)

Publication Number Publication Date
CN106496130A true CN106496130A (zh) 2017-03-15
CN106496130B CN106496130B (zh) 2019-09-20

Family

ID=58291381

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610813031.8A Active CN106496130B (zh) 2016-09-09 2016-09-09 一种甲基酮衍生物及其制备方法与应用

Country Status (1)

Country Link
CN (1) CN106496130B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108456215A (zh) * 2018-05-07 2018-08-28 福州大学 一种控释单线态氧的内过氧化物及其制备和应用
CN111925320A (zh) * 2020-08-12 2020-11-13 武汉大学 一种高效合成多取代2-吡啶酮类化合物的方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101875639A (zh) * 2009-04-29 2010-11-03 中国中化股份有限公司 取代嘧啶醚类化合物及其应用
WO2014049488A1 (en) * 2012-09-28 2014-04-03 Pfizer Inc. Benzamide and heterobenzamide compounds

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101875639A (zh) * 2009-04-29 2010-11-03 中国中化股份有限公司 取代嘧啶醚类化合物及其应用
WO2014049488A1 (en) * 2012-09-28 2014-04-03 Pfizer Inc. Benzamide and heterobenzamide compounds

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
ACS,STN REGISTRY数据库: "RN:1566787-93-6", 《ACS,STN REGISTRY数据库》 *
ACS,STN REGISTRY数据库: "RN:1803876-85-8", 《ACS,STN REGISTRY数据库》 *
ACS,STN REGISTRY数据库: "RN:1806420-55-2", 《ACS,STN REGISTRY数据库》 *
DOUGAL J. RITSON等: "Conversion of Biosynthetic Precursors of RNA to Those of DNA by Photoredox Chemistry", 《JOURNAL OF MOLECULAR EVOLUTION》 *
GANG LI等: "Metal-free methylation of a pyridine N-oxide C-H bond by using peroxides", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 *
LIONEL CARLES等: "2-Pyridones from Cyanoacetamides and Enecarbonyl Compounds: Application to the Synthesis of Nothapodytine B", 《JOURNAL OF ORGANIC CHEMISTRY》 *
QIANG DAI等: "The carbomethylation of arylacrylamides leading to 3-ethyl-3-substituted indolin-2-one by cascade radical addition/cyclization", 《CHEMCOMM COMMUNICATION》 *
YAJIE BAO等: "Copper-Catalyzed Radical Methylation/C-H Amination/Oxidation Cascade for the Synthesis of Quinazolinones", 《THE JOURNAL OF ORGANIC CHEMISTRY》 *
YU SUNG CHUN等: "Cu(OAc)2-Catalyzed Tandem Blaise/Pinner-Type Reaction for One-Pot Synthesis of Pyrimidin-4-ones", 《ORGANIC LETTERS》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108456215A (zh) * 2018-05-07 2018-08-28 福州大学 一种控释单线态氧的内过氧化物及其制备和应用
CN111925320A (zh) * 2020-08-12 2020-11-13 武汉大学 一种高效合成多取代2-吡啶酮类化合物的方法

Also Published As

Publication number Publication date
CN106496130B (zh) 2019-09-20

Similar Documents

Publication Publication Date Title
Dolle et al. A new series of pyridinone derivatives as potent non-nucleoside human immunodeficiency virus type 1 specific reverse transcriptase inhibitors
El‐Hawash et al. Cyanoacetic acid hydrazones of 3‐(and 4‐) Acetylpyridine and some derived ring systems as potential antitumor and anti‐HCV agents
CN101787025B (zh) 取代吴茱萸碱类抗肿瘤和抗真菌化合物及其制备方法
Khoje et al. Synthesis of non-purine analogs of 6-aryl-9-benzylpurines, and their antimycobacterial activities. Compounds modified in the imidazole ring
CN105399757A (zh) 酸敏感型喜树碱-20位去甲斑蝥酸酯衍生物及其抗肿瘤应用
Hocek et al. Cytostatic and antiviral 6-arylpurine ribonucleosides. Part 7: Synthesis and evaluation of 6-substituted purine L-ribonucleosides
Uenishi et al. Syntheses and antitumor activities of D-and L-2′-deoxy-4′-thio pyrimidine nucleosides
CN106496130B (zh) 一种甲基酮衍生物及其制备方法与应用
Colacino et al. Simple and efficient routes for the preparation of isoxazolidinyl nucleosides containing cytosine and 5-methyl-cytosine as new potential anti-HIV drugs
Pathak et al. Baylis–Hillman reaction: Convenient ascending syntheses and biological evaluation of acyclic deoxy monosaccharides as potential antimycobacterial agents
de Champdoré et al. In-water reactivity of nucleosides and nucleotides: one-step preparation and biological evaluation of novel ferrocenyl-derivatives
Elgemeie et al. Synthesis and anti-HIV activity of different novel nonclassical nucleosides
Břehová et al. The efficient synthesis of 2-arylpyrimidine acyclic nucleoside phosphonates using Liebeskind–Srogl cross-coupling reaction
Martirosyan et al. Synthesis of 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2, 4-pyrimidinediones as intermediates for the synthesis of C-azanucleosides
Shimizu et al. The synthesis and biological properties of some aryl bis (nucleosid-5′-yl) phosphates using nucleosides with proven anti-HIV activity
CN103113375A (zh) 一类吡唑并[3,4-d]嘧啶类化合物及其制备方法
Guo et al. Synthesis and antitumor activities of novel bivalent 1-Heterocyclic-β-carbolines linked by alkylamino spacer
Mugnaini et al. Research on L-nucleosides. Synthesis and biological evaluation of a series of L-and D-2′, 3′-dideoxy-3′-[tris (methylthio) methyl]-β-pentofuranosyl nucleosides
Hirama et al. Synthesis and properties of a novel nucleoside derivative possessing a 2, 3, 5, 6-tetraazabenzo [cd] azulene skeleton
KR20200037356A (ko) 피리다지논계 화합물, 그의 제조방법, 약학 조성물 및 용도
CN111533700B (zh) 一种5-取代的尿嘧啶衍生物及其制备方法和应用
CN110256445B (zh) 一种合成dna-pk抑制剂stl127705的方法
CN114920684B (zh) 含硒苯甲酰胺类化合物及其合成方法与应用
CN115322120B (zh) 一类小分子化合物及在制备治疗dhodh介导疾病药物中的用途
CN108078993B (zh) 6-硝基喹唑啉类化合物在制备治疗肺癌药物中的应用

Legal Events

Date Code Title Description
C06 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