3,3-bis(methylthio)-2-methylacryloyl chloride | 170804-95-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯基硫酯
• 英文名称: 3,3-bis(methylthio)-2-methylacryloyl chloride
• 英文别名: 2-Methyl-3,3-bis(methylsulfanyl)prop-2-enoyl chloride
• CAS: 170804-95-2
• 化学式: C₆H₉ClOS₂
• 分子量: 196.722
• InChiKey: NJYZTXRANXVQSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,3-bis(methylthio)-2-methylacryloyl chloride 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 2.5h， 生成 3-(5-Methyl-6-methylsulfanyl-2,4-dioxopyrimidin-1-yl)oxypropyl acetate
  参考文献：
  名称：

  Synthesis and Anti-HIV-1 Activity of a Series of 1-Alkoxy-5-alkyl-6-(arylthio)uracils

  摘要：

  A series of 1-alkoxy-5-alkyl-6-(arylthio)uracils was synthesized and tested for their ability to inhibit HIV-1 replication. Treatment of 2-alkyl-3,3-bis(methylthio)acryloyl chlorides (5a-e) with AgOCN in benzene followed by reaction of the resulting isocyanates 6a-e with an appropriate alkoxyamine gave N-alkoxy-N'-((2-alkyl-3,3-bis(methylthio (10a-z) in good to excellent yields. Cyclization of 10a-z in AcOH containing st catalytic amount of p-TsOH produced 1-alkaxy-5-alkyl-6-(methylthio)uracils (11a-z). Oxidation of 11a-z with 3-chloroperoxybenzoic acid in CH2Cl2 resulted in high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils (12a-x and 12z) and 1-(benzyloxy)-6-(methylsulfinyl)thymine (12y), which were subsequently reacted with an appropriate arenethiol in ethanolic NaOH solution to afford 1-alkoxy-5-alkyl-6-(arylthio)uracils (14-49). Substitution at the 3- and 5-positions of the C-6-(phenylthio) ring by two methyl groups significantly increased its original anti-HIV-l activity (EC50: 6-((3,5-dimethylphenyl)thio)-5-isopropyl-1-propoxyuracil (18), 0.064 mu M; 6-((3,5-dimethylphenyl)thio)-1-(3-hydroxypropoxy)-5-isopropyluracil (23), 0.19 mu M). Among the various alkoxy substituents at the N-1, the propoxy group was the most beneficial for improving the anti-HIV-1 activity. The 1-propoxy derivative 18 proved to be the most potent inhibitor of HIV-1 replication, followed by the 1-(3-hydroxypropoxy) derivative 23. Introduction of an isopropyl group at C-5 of the uracil base also remarkably enhanced the activity. When compound 18 was incubated with a rat liver homogenate preparation, no metabolite was observed, thus confirming the metabolic stability of the N-O bond in these 1-alkoxyuracils.

  DOI：

  10.1021/jm9607921
• 作为产物：
  描述：

  ethyl 3,3-bis(methylthio)-2-methylacrylate 在 氢氧化钾 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 苯 为溶剂， 反应 6.0h， 生成 3,3-bis(methylthio)-2-methylacryloyl chloride
  参考文献：
  名称：

  Synthesis and Anti-HIV-1 Activity of a Series of 1-Alkoxy-5-alkyl-6-(arylthio)uracils

  摘要：

  A series of 1-alkoxy-5-alkyl-6-(arylthio)uracils was synthesized and tested for their ability to inhibit HIV-1 replication. Treatment of 2-alkyl-3,3-bis(methylthio)acryloyl chlorides (5a-e) with AgOCN in benzene followed by reaction of the resulting isocyanates 6a-e with an appropriate alkoxyamine gave N-alkoxy-N'-((2-alkyl-3,3-bis(methylthio (10a-z) in good to excellent yields. Cyclization of 10a-z in AcOH containing st catalytic amount of p-TsOH produced 1-alkaxy-5-alkyl-6-(methylthio)uracils (11a-z). Oxidation of 11a-z with 3-chloroperoxybenzoic acid in CH2Cl2 resulted in high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils (12a-x and 12z) and 1-(benzyloxy)-6-(methylsulfinyl)thymine (12y), which were subsequently reacted with an appropriate arenethiol in ethanolic NaOH solution to afford 1-alkoxy-5-alkyl-6-(arylthio)uracils (14-49). Substitution at the 3- and 5-positions of the C-6-(phenylthio) ring by two methyl groups significantly increased its original anti-HIV-l activity (EC50: 6-((3,5-dimethylphenyl)thio)-5-isopropyl-1-propoxyuracil (18), 0.064 mu M; 6-((3,5-dimethylphenyl)thio)-1-(3-hydroxypropoxy)-5-isopropyluracil (23), 0.19 mu M). Among the various alkoxy substituents at the N-1, the propoxy group was the most beneficial for improving the anti-HIV-1 activity. The 1-propoxy derivative 18 proved to be the most potent inhibitor of HIV-1 replication, followed by the 1-(3-hydroxypropoxy) derivative 23. Introduction of an isopropyl group at C-5 of the uracil base also remarkably enhanced the activity. When compound 18 was incubated with a rat liver homogenate preparation, no metabolite was observed, thus confirming the metabolic stability of the N-O bond in these 1-alkoxyuracils.

  DOI：

  10.1021/jm9607921

文献信息

• Synthesis of 6-substituted 1-alkoxy-5-alkyluracils
  作者：Dae-Kee Kim、Young-Woo Kim、Key H. Kim

  DOI：10.1002/jhet.5570340148

  日期：1997.1

  Synthesis of 6-substituted 1-alkoxy-5-alkyluracils 2a-c have been achieved from readily accessible 2-alkyl-3,3-di(methylthio)acryloyl chlorides 4a,b in high overall yields. Treatment of 4a,b with silver cyanate followed by reaction of the resulting isocyanates 5a,b with an appropriate alkoxyamine afforded N-alkoxy-N′-[2-alkyl-3,3-di(methylthio)acryloyl]ureas 6a,b in 85–88% yields. Cyclization of 6a

  从易于获得的2-烷基-3，3-二（甲硫基）丙烯酰氯4a，b已经以高的总收率实现了6-取代的1-烷氧基-5-烷基尿嘧啶2a-c的合成。的治疗4A，4B与氰酸银，然后将所得的异氰酸酯的反应5a，5b中与得到适当的烷氧基胺ñ -烷氧基- ñ ' - [2-烷基3,3-二（甲硫基）丙烯酰基]脲6A，6B在85–88％的产量。6a，b在含甲磺酸的乙酸中环化，然后用3-氯过氧苯甲酸氧化，得到高产率的1-烷氧基-5-烷基-6-（甲基磺酰基）尿嘧啶9a，b。9a，b与叠氮化钠，苯硫醇或苯硒醇的亲核加成消除反应生成6-叠氮基-1-丁氧基胸腺嘧啶（2a，98％），5-乙基-1-（2-苯氧基乙氧基）-6-（苯硫基）尿嘧啶（2b，95％）或5-乙基-1-（2-苯氧基乙氧基）-6-（苯基硒烯基）尿嘧啶（2c，91％）。
• A convenient approach to the synthesis of 6-substituted 1,5-dialkyluracils and -2-thiouracils
  作者：Dae-Kee Kim、Young-Woo Kim、Jongsik Gam、Jinsoo Lim、Key H Kim

  DOI：10.1016/0040-4039(95)01238-d

  日期：1995.8

  A general and convenient approach to the synthesis of 6-substituted 1,5-dialkyluracils and 2-thiouracils via 1,5-dialkyl-6-(methylsulfonyl) uracils 1 and 1,5-dialkyl-6-(methylsulfinyl)-2-thiouracils 2, respectively, has been described. The compounds 1 and 2 were synthesized from ethyl 2-alkyl-3,3-di(methylthio)acrylates 3 in live steps in good yields.
• Synthesis and Anti-HIV-1 Activity of a Series of 1-Alkoxy-5-alkyl-6-(arylthio)uracils
  作者：Dae-Kee Kim、Jongsik Gam、Young-Woo Kim、Jinsoo Lim、Hun-Taek Kim、Key H. Kim

  DOI：10.1021/jm9607921

  日期：1997.7.1

  A series of 1-alkoxy-5-alkyl-6-(arylthio)uracils was synthesized and tested for their ability to inhibit HIV-1 replication. Treatment of 2-alkyl-3,3-bis(methylthio)acryloyl chlorides (5a-e) with AgOCN in benzene followed by reaction of the resulting isocyanates 6a-e with an appropriate alkoxyamine gave N-alkoxy-N'-((2-alkyl-3,3-bis(methylthio (10a-z) in good to excellent yields. Cyclization of 10a-z in AcOH containing st catalytic amount of p-TsOH produced 1-alkaxy-5-alkyl-6-(methylthio)uracils (11a-z). Oxidation of 11a-z with 3-chloroperoxybenzoic acid in CH2Cl2 resulted in high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils (12a-x and 12z) and 1-(benzyloxy)-6-(methylsulfinyl)thymine (12y), which were subsequently reacted with an appropriate arenethiol in ethanolic NaOH solution to afford 1-alkoxy-5-alkyl-6-(arylthio)uracils (14-49). Substitution at the 3- and 5-positions of the C-6-(phenylthio) ring by two methyl groups significantly increased its original anti-HIV-l activity (EC50: 6-((3,5-dimethylphenyl)thio)-5-isopropyl-1-propoxyuracil (18), 0.064 mu M; 6-((3,5-dimethylphenyl)thio)-1-(3-hydroxypropoxy)-5-isopropyluracil (23), 0.19 mu M). Among the various alkoxy substituents at the N-1, the propoxy group was the most beneficial for improving the anti-HIV-1 activity. The 1-propoxy derivative 18 proved to be the most potent inhibitor of HIV-1 replication, followed by the 1-(3-hydroxypropoxy) derivative 23. Introduction of an isopropyl group at C-5 of the uracil base also remarkably enhanced the activity. When compound 18 was incubated with a rat liver homogenate preparation, no metabolite was observed, thus confirming the metabolic stability of the N-O bond in these 1-alkoxyuracils.