2-环丙基-2-羰基乙酸钾 | 56512-18-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: 2-环丙基-2-羰基乙酸钾
• 英文名称: potassium cyclopropylglyoxylate
• 英文别名: potassium 2-cyclopropyl-2-oxoacetate；potassium;2-cyclopropyl-2-oxoacetate
• CAS: 56512-18-6
• 化学式: C₅H₅O₃*K
• 分子量: 152.191
• InChiKey: BIHOEOFKAILDIR-UHFFFAOYSA-M

物化性质

• 熔点：
  241 °C (decomp)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.28
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-环丙基-2-羰基乙酸钾 在 Pichia pastoris formate dehydrogease 、 Thermoactinomyces intermedius leucine dehydrogenase 、 β-烟酰胺腺嘌呤二核苷酸 、 甲酸铵 、 sodium hydroxide 、 1,4-二巯基-2,3-丁二醇 作用下， 以 水 为溶剂， 以99%的产率得到(S)-2-amino-2-cyclopropylacetic acid
  参考文献：
  名称：

  Preparation of (S)-1-Cyclopropyl-2-methoxyethanamine by a Chemoenzymatic Route Using Leucine Dehydrogenase

  摘要：

  (S)-1-Cyclopropyl-2-methoxyethanamine is a key chiral intermediate for the synthesis of a corticotropin-releasing factor-1(CRF-1) receptor antagonist. Resolution of the racemic amine by transaminase from Vibrio fluvalis gave a 38% yield of the S-amine with 53% ee. Resolution by lipase-catalyzed acylation provided the S-amine in 35% yield with 91% ee. With limited success of these resolution approaches, an efficient chemo-enzymatic route to (S)-1-cyclopropyl-2-methoxyethanamine was devised starting from methylcyclopropyl ketone. Permanganate oxidation of the ketone gave cyclopropylglyoxylic acid, which was converted to (S)-cyclopropylglycine by reductive amination using leucine dehydrogenase from Thermoactinomyces intermedius with NADH cofactor recycling by formate dehydrogenase from Pichia pastoris. Both enzymes were cloned and expressed in recombinant E. coli. (S)-Cyclopropylglycine obtained from enzymatic reductive amination was isolated as the N-Boc derivative and converted to the desired amine by reduction, methylation, and deprotection to give (S)1-cyclopropyl-2-methoxyethanamine in 62% overall yield from cyclopropylglyoxylic acid, with no detectable R-enantiomer.

  DOI：

  10.1021/op2003562
• 作为产物：
  描述：

  环丙甲基酮 在 氢氧化钾 、 potassium permanganate 作用下， 以 水 为溶剂， 反应 1.0h， 生成 2-环丙基-2-羰基乙酸钾
  参考文献：
  名称：

  Synthesis and chemical transformations of 2-cyclopropyl-2-diazoacetates

  摘要：

  2-环丙基-2-重氮乙酸甲酯是由乙酰环丙烷通过几个化学步骤合成的，总产率约 55%。其铜或铑催化的脱重氮反应仅通过生成的环丙基（甲氧基羰基）卡宾分子内异构化为1-甲氧基羰基环丁烯进行，无论是否存在不饱和化合物。然而，在丙烯酸酯或应变环烯烃的存在下，这种重氮酯缓慢参与1,3-偶极环加成反应，得到环丙基取代的吡唑啉甲酸酯，在1-吡唑啉的情况下，它很容易失去氮分子，选择性地生成1-环丙基环丙烷甲酸酯衍生物。

  DOI：

  10.1007/s11172-007-0234-6

文献信息

• POLYFLUORINATED COMPOUNDS ACTING AS BRUTON TYROSINE KINASE INHIBITORS
  申请人：He Wei

  公开号：US20160200730A1

  公开（公告）日：2016-07-14

  Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.

  本文描述了一种新型的多氟取代吡唑嘧啶化合物或其盐。这些化合物是布鲁顿酪氨酸激酶（BTK）抑制剂。这些化合物可能具有更好的BTK抑制选择性和药代动力学特性。本文披露了这些化合物的合成方法。本文还披露了多氟取代苯甲酮和取代苯氧基苯的新型合成方法。还披露了包括上述BTK抑制剂的药物组合物。本发明还涉及包含上述化合物作为活性成分的药物配方。本发明还包括通过给予BTK抑制剂及其配方来治疗和抑制自身免疫疾病、过敏性疾病、炎症性疾病和癌症的治疗方法。
• 2-Cyclopropaneglyoxylic acid: a probe for the mechanism of hydrogen transfer by lactate dehydrogenase and by N-benzyl-1,4-dihydronicotinamide
  作者：Derek C. Nonhebel、Stefan T. Orszulik、Colin J. Suckling

  DOI：10.1039/c39820001146

  日期：——

  Reduction of cyclopropaneglyoxylic acid by lactate dehydrogenase and by model systems for both lactate and alcohol dehydrogenases occurs without cleavage of the three-membered ring implying that radical intermediates are improbable in these reactions.

  通过乳酸脱氢酶以及通过模型系统对乳酸和醇脱氢酶还原环丙烷乙醛酸而没有三元环的裂解，这意味着自由基中间体在这些反应中是不可能的。
• L-Lactate dehydrogenase: substrate specificity and use as a catalyst in the synthesis of homochiral 2-hydroxy acids
  作者：Mahn Joo. Kim、George M. Whitesides

  DOI：10.1021/ja00217a044

  日期：1988.4

  This note compares the substrate specificity of D-lactate dehydrogenase (D-LDH, EC 1.1.1.28) to that of L-lactate dehydrogenase (L-LDH, EC 1.1.1.27), illustrates three procedures that use D-LDH in synthesis and two methods for recycling NADH, and provides experimental details illustrating the use of D-LDH in organic synthesis.

  本说明比较了 D-乳酸脱氢酶 (D-LDH, EC 1.1.1.28) 与 L-乳酸脱氢酶 (L-LDH, EC 1.1.1.27) 的底物特异性，说明了在合成中使用 D-LDH 的三种程序和两种回收 NADH 的方法，并提供实验细节，说明 D-LDH 在有机合成中的用途。
• Practical Syntheses of Both Enantiomers of Cyclopropylglycine and of Methyl 2-Cyclopropyl-2-N-Boc-iminoacetate
  作者：Oleg V. Larionov、Armin de Meijere

  DOI：10.1002/adsc.200606038

  日期：2006.6

  cyclopropyl methyl ketone has been elaborated. Enzymatic hydrolysis of the N-Boc-protected methyl ester of cyclopropylglycine 9 with the inexpensive enzyme papain from Carica papaya affords both enantiomers of cyclopropylglycine (8) with enantiomeric excesses of 99 % or better after deprotection under acidic conditions. Furthermore, the new cyclopropyl group-containing building block methyl 2-cyclopr

  已详细说明了从便宜的环丙基甲基酮轻松合成三克外消旋环丙基甘氨酸的方法。用来自番木瓜的廉价木瓜蛋白酶酶解环丙基甘氨酸9的N -Boc保护的甲酯，在酸性条件下脱保护后，提供环丙基甘氨酸（8）的两种对映异构体，其对映体过量为99％或更高。此外，通过N制备新的含环丙基基团的2-环丙基-2- N -Boc-亚氨基乙酸甲酯（13）1,8-二氮杂双环[5.4.0]十一碳-7-烯（DBU）进行氯化-氯化反应，然后进行脱氯化氢反应。向13个亲核试剂中添加亲核试剂可方便地获得不寻常的，正交双保护的α，α-二氨基酸衍生物和刚性肽骨架的有趣组分。
• Synthesis and Radical Polymerization of Various 2-Cyclopropylacrylates
  作者：Armin de Meijere、Viktor Bagutski、Frank Zeuner、Urs Karl Fischer、Volker Rheinberger、Norbert Moszner

  DOI：10.1002/ejoc.200400132

  日期：2004.9

  spectrometry and elemental analysis. The radical homopolymerizations of 1a−n were carried out with 2,2′-azabisisobutyronitrile (AIBN) as initiator in chlorobenzene at 65 °C. The highest polymer yields were obtained in the polymerizations of 1f and 1h or 1k and 1l, i.e. from monomers with an annelated five- or six-membered ring. In the case of 1h and 1k, both the polymer yields (99 and 98%, respectively) and

  通过应用标准转化，例如从醛形成氰醇、醇解为 α-羟基羧酸酯、α-氧代羧酸的氧化和 Wittig 亚甲基化，从容易获得的前体合成了十四种具有各种取代基 R1-R5 的新型 2-环丙烷基丙烯酸酯 1a-n酯。总产率为 33% 至 54%。开发了一种将环丙二甲酸二甲酯水解成相应半酯的新方法。α-氧代羧酸盐 7g-n 是通过四乙酸二铑催化烯烃 8g-n 与重氮丙酮酸甲酯或乙酯的环丙烷化反应制备的，产率为 32-58%。单体 1a-n 通过 1H、13C NMR 光谱、质谱和元素分析进行​​表征。1a-n 的自由基均聚是用 2 进行的，2'-氮杂二异丁腈 (AIBN) 作为引发剂在 65 °C 的氯苯中。在 1f 和 1h 或 1k 和 1l 的聚合中获得最高的聚合物产率，即来自具有退火五元或六元环的单体。在 1h 和 1k 的情况下，聚合物产率（分别为 99% 和 98%）以及 57 和 93 °C