N-phthalimide l-valinyl chloride | 5511-73-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-phthalimide l-valinyl chloride
• 英文别名: (S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanoyl chloride；(S)-N-Phthaloylvalylchlorid；(2S)-2-(1,3-dioxoisoindol-2-yl)-3-methylbutanoyl chloride
• CAS: 5511-73-9
• 化学式: C₁₃H₁₂ClNO₃
• mdl: MFCD02170453
• 分子量: 265.696
• InChiKey: NCWARQGSAYOFNE-JTQLQIEISA-N

物化性质

• 熔点：
  80-82 °C
• 沸点：
  366.1±25.0 °C(Predicted)
• 密度：
  1.351±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-phthalimide l-valinyl chloride 在 邻羧基苯乙酸 作用下， 反应 6.0h， 以720 mg的产率得到2-(2-methylprop-1-enyl)-2-benzazole-1,3-dione
  参考文献：
  名称：

  Chiron based synthesis of isocoumarins: reactivity of α-substituted carboxylic acids

  摘要：

  The asymmetric synthesis of a novel (S)-isocoumarin has been attempted in a single step by the coupling of homophthalic acid with (S)-N-protected amino acids and alpha-chloroacids at high temperature by exploiting a chiral pool methodology. The coupling of homophthalic acid with N-protected (S)-amino acids gave exclusion of the carboxyl/alkyl group. However, coupling of homophthalic acid with alpha-chloro-acids afforded asymmetric isocoumarins in high yield. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2014.03.019
• 作为产物：
  描述：

  L-缬氨酸 在 氯化亚砜 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 N-phthalimide l-valinyl chloride
  参考文献：
  名称：

  基于N-邻苯二甲酰-α-氨基酸的新型酰胺的合成

  摘要：

  N-邻苯二甲酰基碳链α-氨基酸的衍生物在标准条件下采用邻苯二甲酰酸酐合成。通过热方法优化反应以获得这些N-邻苯二甲酰基氨基酸的酰胺，结果显示转化倾向于而非氨基化。N-邻苯二甲酰基-α-氨基酸的目标酰胺通过在二氯甲烷中与相应的酸氯酐进行酰化获得。这些结果与在非极性溶剂（苯）中进行的类似酰化结果进行了比较。确定了反应方向依赖于酰化持续时间和所用氨基的量。还找到了相应的N-邻苯二甲酰基-α-氨基酸酰胺和不对称邻苯二甲酸二酰胺的形成条件。值得注意的是，二酰胺的形成与氨基的等效量和反应时间呈正比，这使得能够在一个反应器中有针对性地控制合成。

  DOI：

  10.21608/ejchem.2021.48494.2990

文献信息

• Trifluoroborane-Catalyzed C–H Functionalization/S–H Insertion Reaction: Construction of N,S-Acetal Quaternary Centers
  作者：Yan Cai、Haihong Ge、Weize Sun、Zhiwei Miao

  DOI：10.1055/s-0034-1380384

  日期：2015.6

  The trifluoroborane-catalyzed C–H functionalization/S–H insertion reaction of α-diazophosphonates with thiols has been developed. A plausible reaction mechanism has been proposed to understand the combined reaction. This process provides straightforward access to N,S-acetals containing quaternary centers in moderate to good yields and chemoselectivity.

  三氟硼烷催化的α-重氮磷酸酯与硫醇的C-H官能化/S-H插入反应已经被开发出来。已经提出了一个合理的反应机理来理解这个复合反应。这个过程以中等到良好的产率和化学选择性提供了直接访问含有季铵中心的N,S-缩醛。
• [EN] CHEMICAL COMPOUNDS AS H-PGDS INHIBITORS<br/>[FR] COMPOSÉS CHIMIQUES UTILISÉS EN TANT QU'INHIBITEURS DE H-PGDS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018229629A1

  公开（公告）日：2018-12-20

  A compound of formula (I) wherein R1, R2, R3, R4, X, Y, and A are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne muscular dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  根据本发明，化合物公式(I)中，R1、R2、R3、R4、X、Y和A的定义如所述。本发明的化合物是造血前列腺素D合酶（H-PGDS）的抑制剂，可用于治疗杜氏肌营养不良症。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物抑制H-PGDS活性和治疗相关疾病的方法。
• Enantioselective Aldol and Michael Additions of Achiral Enolates in the Presence of Chiral Lithium Amides and Amines
  作者：Eusebio Juaristi、Albert K. Beck、Jesper Hansen、Thomas Matt、Triptikumar Mukhopadhyay、Malgorzata Simson、Dieter Seebach

  DOI：10.1055/s-1993-26041

  日期：——

  It is now well established that lithium enolates and analogous derivatives generally exist as complex structures held together by noncovalent bonds ("supramolecules"). In particular, Li enolates aggregate to give dimers, tetramers, and higher oligomers, whose metal centers may be complexed by solvent molecules or chelating ligands. In addition, the anionoid part of the enolates may hydrogen-bond to weak acids such as secondary amines. Furthermore, such supramolecules can be product-forming species in synthetic reactions of Li enolates. This paper describes our observations of the temporary incorporation of chiral amines or chiral lithium amides into achiral lithium enolate aggregates (an interaction which is simply broken during aqueous workup!) to give enantiomerically enriched products. In particular, enantioselective aldol and Michael additions between achiral enolates and achiral aldehydes or achiral nitroolefins have been achieved in the presence of several chiral amines (or their lithium amides) derived from (S)-valine or (R,R)-tartaric acid. Finally, this report demonstrates the potential usefulness in asymmetric synthesis of ortho lithiation directed by chiral α-aminoalkoxides.

  目前已经充分确定，锂烯醇盐及其类似衍生物通常以非共价键结合而成的复杂结构（“超分子”）存在。特别是，锂烯醇盐聚集形成二聚体、四聚体和高阶寡聚体，其金属中心可能被溶剂分子或螯合配体络合。此外，烯醇盐的阴离子部分可能与二级胺等弱酸形成氢键。而且，这些超分子在锂烯醇盐的合成反应中可能是产物形成物种。本文描述了我们观察到的将手性胺或手性锂酰胺暂时掺入非手性锂烯醇盐聚集体（在水中处理时这种相互作用被简单破坏！）从而产生手性富集产物的现象。特别是，在几种由(S)-缬氨酸或(R,R)-酒石酸衍生的手性胺（或它们的锂酰胺）存在下，实现了非手性烯醇盐与非手性的醛或非手性硝基烯烃的立体选择性羟醛缩合反应和迈克尔加成反应。最后，本报告展示了手性α-氨基烷氧基导向的邻位锂化在对映选择性合成中的潜在应用价值。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2020095215A1

  公开（公告）日：2020-05-14

  A compound of formula (I), wherein Ar1, R21, R23, R24, R25, R26, R27, A, X, Y and W are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne muscular dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明的化合物具有式（I），其中Ar1，R21，R23，R24，R25，R26，R27，A，X，Y和W如本文所定义。本发明的化合物是造血前列腺素D合酶（H-PGDS）的抑制剂，可用于治疗杜兴氏肌肉营养不良。因此，该发明进一步涉及包含本发明化合物的药物组合物。该发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制H-PGDS活性和治疗相关疾病的方法。
• 3-Amino-1-methyl-1<i>H</i>-pyridin-2-one-Directed Pd^II Catalysis: C(sp³)–H Activated Diverse Arylation Reaction
  作者：Tanmay K. Pati、Sudipto Debnath、Mrinalkanti Kundu、Uttam Khamrai、Dilip K. Maiti

  DOI：10.1021/acs.orglett.8b01618

  日期：2018.7.6

  A new bidentate directing group, 3-amino-1-methyl-1H-pyridin-2-one, is introduced to achieve a powerful PdII metallacycle for selective γ-C(sp3)–H activation and arylation of aromatic and aliphatic carboxylic acid derivatives. The versatility of the directing group is validated for remote arylation of β-C(sp3)–H, β-C(sp2)–H, and γ-C(sp2)–H to achieve therapeutically important 2-pyridone analogues and

  引入了一个新的双齿指导基团3-氨基-1-甲基-1 H-吡啶-2--2-，以实现强大的Pd II金属环，从而选择性地活化和芳族和脂族的γ-C（sp 3）-H芳基化羧酸衍生物。验证了该指导组的多功能性，可实现β-C（sp 3）–H，β-C（sp 2）–H和γ-C（sp 2）–H的远程芳基化，从而获得具有重要治疗意义的2-吡啶酮类似物和芳基酸合成子。通过无痕除去导向基团以回收导向元素和羧酸，使该方法更加有趣。