acetic acid 4,4-diethoxy-1,1-dimethyl-2-oxo-butyl ester | 463335-45-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: acetic acid 4,4-diethoxy-1,1-dimethyl-2-oxo-butyl ester
• 英文别名: Acetic acid 4,4-diethoxy-1,1-dimethyl-2-oxobutyl ester；(5,5-diethoxy-2-methyl-3-oxopentan-2-yl) acetate
• CAS: 463335-45-7
• 化学式: C₁₂H₂₂O₅
• 分子量: 246.304
• InChiKey: FJLNSJDWBNDVER-UHFFFAOYSA-N

物化性质

• 沸点：
  312.5±32.0 °C(Predicted)
• 密度：
  1.024±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  acetic acid 4,4-diethoxy-1,1-dimethyl-2-oxo-butyl ester 在 palladium diacetate 、 三苯基膦 乙醇 、 sodium methylate 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 17.0h， 生成 2-[3-(3-chloro-4-fluoro-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol
  参考文献：
  名称：

  Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach

  摘要：

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.

  DOI：

  10.1021/jo050741o
• 作为产物：
  描述：

  3-羟基-3-甲基-2-丁酮 在 4-二甲氨基吡啶 、 三氟化硼乙醚 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 25.45h， 生成 acetic acid 4,4-diethoxy-1,1-dimethyl-2-oxo-butyl ester
  参考文献：
  名称：

  Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach

  摘要：

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.

  DOI：

  10.1021/jo050741o

文献信息

• [EN] IMIDAZO-PYRIMIDINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS<br/>[FR] DERIVES D'IMIDAZO-PYRIMIDINE UTILISES COMME LIGANDS POUR LES RECEPTEURS GABA
  申请人：MERCK SHARP & DOHME

  公开号：WO2002074772A1

  公开（公告）日：2002-09-26

  A class of 3-phenylimidazo[1,2-a]pyrimidine derivatives, substituted at the meta position of the phenyl ring by a directly attached, optionally halo- and/or cyano-substituted aryl or heteroaryl group, and further substituted on the phenyl ring by one or two fluorine atoms, are selective ligands for GABAA receptors, in particular having good affinity for the α2 and/or α3 and/or α5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类3-苯基咪唑[1,2-a]嘧啶衍生物，取代苯环的间位，直接连接一个可选择的卤素和/或氰基取代的芳基或杂环基团，并在苯环上进一步取代一个或两个氟原子，是选择性的GABAA受体配体，特别是对其α2和/或α3和/或α5亚单位具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑、惊厥和认知障碍具有益处。
• [EN] IMIDAZO-PYRIMIDINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS<br/>[FR] DERIVES D'IMIDAZO-PYRIMIDINE COMME LIGANDS POUR LES RECEPTEURS GABA
  申请人：MERCK SHARP & DOHME

  公开号：WO2002074773A1

  公开（公告）日：2002-09-26

  A class of 3-phenylimidazo[1,2-a]pyrimidine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a -NH- linkage, and further substituted on the phenyl ring by alkyl, trifluoromethyl, alkoxy or one or two halogen atoms, especially fluoro, are selective ligands for GABAA receptors, in particular having good affinity for the a2 and/or a3 and/or a5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类3-苯基咪唑并[1,2-a]嘧啶衍生物，苯环的间位被取代为可选择取代的芳基或杂环基，该基团直接连接或通过氧原子或-NH-键桥接，并且苯环上进一步取代为烷基，三氟甲基，烷氧基或一个或两个卤素原子，特别是氟原子。这些化合物是GABAA受体的选择性配体，特别是对其中的a2和/或a3和/或a5亚基具有良好的亲和力，因此有助于治疗和/或预防中枢神经系统的不良症状，包括焦虑，抽搐和认知障碍。
• Imidazo-pyrimidine derivatives as ligands for gaba receptors
  申请人：——

  公开号：US20020193385A1

  公开（公告）日：2002-12-19

  A class of 3-phenylimidazo[1,2-&agr;]pyrimidine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, and further substituted on the phenyl ring by alkyl, trifluoromethyl, alkoxy or one or two halogen atoms, especially fluoro, are selective ligands for GABA A receptors, in particular having good affinity for the &agr;2 and/or &agr;3 and/or &agr;5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类3-苯基咪唑[1,2-&agr;]嘧啶衍生物，苯环的间位被取代，取代基可以是直接连接或通过氧原子或-NH-键桥接的取代芳基或杂环芳基，苯环上进一步被取代为烷基，三氟甲基，烷氧基或一个或两个卤素原子，特别是氟，是GABAA受体的选择性配体，特别是对其中的&agr;2和/或&agr;3和/或&agr;5亚基具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑，惊厥和认知障碍具有益处。
• Imidazo-pyrimidine derivatives as ligands for GABA receptors
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US07030128B2

  公开（公告）日：2006-04-18

  A class of imidazo[1,2-α]pyrimidine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, are selective ligands for GABAA receptors, in particular having good affinity for the α2 and/or α3 and/or α5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类在3位取代了一个选择性取代的五元或六元杂环芳香环的咪唑[1,2-α]嘧啶衍生物是GABAA受体的选择性配体，尤其对其中的α2和/或α3和/或α5亚基具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑、抽搐和认知障碍具有益处。
• Imidazo[1,2<i>-a</i>]pyrimidines as Functionally Selective and Orally Bioavailable GABA_Aα2/α3 Binding Site Agonists for the Treatment of Anxiety Disorders
  作者：Simon C. Goodacre、Leslie J. Street、David J. Hallett、James M. Crawforth、Sarah Kelly、Andrew P. Owens、Wesley P. Blackaby、Richard T. Lewis、Joanna Stanley、Alison J. Smith、Pushpinder Ferris、Bindi Sohal、Susan M. Cook、Andrew Pike、Nicola Brown、Keith A. Wafford、George Marshall、José L. Castro、John R. Atack

  DOI：10.1021/jm051065l

  日期：2006.1.1

  A series of high-affinity GABA(A) agonists with good oral bioavailability in rat and dog and functional selectivity for or the GABA(A)alpha 2 and -alpha 3 subtypes is reported. The 7-trifluoroinethylimidazopyrimidine 14g and the 7-propan-2-olimidazopyrimidine 14k are anxiolytic in both conditioned and unconditioned animal models of anxiety with minimal sedation observed at full BZ binding site occupancy.