di-t-butyl 2-(4-methyl-2-nitrophenyl)malonate | 1134197-59-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: di-t-butyl 2-(4-methyl-2-nitrophenyl)malonate
• 英文别名: bis(1,1-dimethylethyl) (4-methyl-2-nitrophenyl)propanedioate；di-tert-butyl 2-(4-methyl-2-nitrophenyl)malonate；ditert-butyl 2-(4-methyl-2-nitrophenyl)propanedioate
• CAS: 1134197-59-3
• 化学式: C₁₈H₂₅NO₆
• 分子量: 351.4
• InChiKey: MWEQEUFSGLLJAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  di-t-butyl 2-(4-methyl-2-nitrophenyl)malonate 在 钯 氢气 作用下， 以 乙酸乙酯 为溶剂， 25.0 ℃ 、13.51 MPa 条件下， 反应 20.0h， 以to afford the title compound as a colourless oil (606 mg, 100%)的产率得到bis(1,1-dimethylethyl) (2-amino-4-methylphenyl)propanedioate
  参考文献：
  名称：

  Compounds Which Have Activity at M1 Receptor and Their Uses in Medicine

  摘要：

  提供化学式(I)的化合物或其盐： 其中R4、R5、R6、Q、A、Y和R的定义如说明书所述。本发明还公开了将该化合物用作药物治疗精神疾病、认知障碍和阿尔茨海默病以及制造药物的用途。本发明还公开了包含该化合物的制药组合物。

  公开号：

  US20120316196A1
• 作为产物：
  描述：

  丙二酸二叔丁酯 、 4-氟-3-硝基甲苯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 以65.5%的产率得到di-t-butyl 2-(4-methyl-2-nitrophenyl)malonate
  参考文献：
  名称：

  MUSCARINIC RECEPTOR AGONISTS, COMPOSITIONS, METHODS OF TREATMENT THEREOF, AND PROCESSES FOR PREPARATION THEREOF-176

  摘要：

  式1的化合物，或其药用可接受的盐：其中X、R1、R2、R3、R4、R5、n、m和p的定义如规范中所述，以及包括这些化合物的盐和药物组合物已经准备好。它们在治疗中很有用，特别是在疼痛管理中。

  公开号：

  US20090221642A1

文献信息

• [EN] COMPOUNDS WHICH HAVE ACTIVITY AT M1 RECEPTOR AND THEIR USES IN MEDICINE<br/>[FR] COMPOSÉS PRÉSENTANT UNE ACTIVITÉ AU NIVEAU DU RÉCEPTEUR M1 ET LEURS UTILISATIONS EN MÉDECINE
  申请人：GLAXO GROUP LTD

  公开号：WO2009037294A1

  公开（公告）日：2009-03-26

  Compounds of formula (I) or a salt thereof are provided: wherein R4, R5, R6, Q, A, Y and R are as defined in the description. Uses of the compounds as medicaments and in the manufacture of medicaments for treating psychotic disorders, cognitive impairments and Alzheimer's Disease are disclosed. The invention further discloses pharmaceutical compositions comprising the compounds.

  提供具有公式(I)或其盐的化合物：其中R4、R5、R6、Q、A、Y和R按描述定义。披露了这些化合物作为药物的使用和在制造用于治疗精神病性障碍、认知障碍和阿尔茨海默病药物中的应用。本发明还公开了包含这些化合物的药物组合物。
• Compounds which have activity at M1 receptor and their uses in medicine
  申请人：Cooper David Gwyn

  公开号：US20100204272A1

  公开（公告）日：2010-08-12

  Compounds of formula (I) or a salt thereof are provided: wherein R 4 , R 5 , R 6 , Q, A, Y and R are as defined in the description. Uses of the compounds as medicaments and in the manufacture of medicaments for treating psychotic disorders, cognitive impairments and Alzheimer's Disease are disclosed. The invention further discloses pharmaceutical compositions comprising the compounds.

  本发明提供了化学式(I)的化合物或其盐：其中R4，R5，R6，Q，A，Y和R的定义如说明书中所定义。本发明还揭示了将该化合物用作药物以及制造用于治疗精神障碍，认知障碍和阿尔茨海默病的药物的用途。本发明还揭示了包含该化合物的制药组合物。
• The discovery of a series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles as highly brain penetrant, selective muscarinic M1 agonists
  作者：Dale J. Johnson、Ian T. Forbes、Steve P. Watson、Vincenzo Garzya、Graeme I. Stevenson、Graham R. Walker、Harminder S. Mudhar、Sean T. Flynn、Paul A. Wyman、Paul W. Smith、Graham S. Murkitt、Adam J. Lucas、Claudette R. Mookherjee、Jeannette M. Watson、Jane E. Gartlon、Andrea M. Bradford、Fiona Brown

  DOI：10.1016/j.bmcl.2010.07.097

  日期：2010.9

  A series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles are reported which were found to be potent and selective muscarinic M-1 agonists. By control of the physicochemical characteristics of the series, particularly the lipophilicity, compounds with good metabolic stability and excellent brain penetration were identified. An exemplar of the series was shown to be pro-cognitive in the novel object recognition rat model of temporal induced memory deficit. (c) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of Substituted t-Butyl 3-Alkyloxindole-3-carboxylates from Di-t-butyl (2-Nitrophenyl)malonates
  作者：Takaaki Sumiyoshi、Yu-suke Yamai、Akio Tanaka、Tatsuo Yajima、Kyoji Ishida、Itaru Natsutani、Shinichi Uesato、Yasuo Nagaoka

  DOI：10.3987/com-17-s(t)2

  日期：——

  Using a novel tandem reduction-cyclization, we synthesized t-butyl 3-alkyloxindole-3-carboxylates from the di-t-butyl 2-alkyl-2-(2-nitrophenyl)malonate. Introduction of an alpha-substituent to the di-t-butyl 2-(2-nitrophenyl)-malonates and addition of acid promoted reactivity. This methodology was successfully applied to gram-scale-synthesis of the t-butyl 3-methyloxindole-3-carboxylate 1 and 3-hydroxyrnethy1-3-methyloxindole 2 without silica gel column chromatography.
• Efficient Synthesis of t-Butyl 3-Alkyl-N-hydroxyoxindole-3-carboxylates from Di-t-butyl 2-nitrophenylmalonates
  作者：Takaaki Sumiyoshi、Yu-suke Yamai、Kyoji Ishida、Itaru Natsutani、Shinichi Uesato、Yasuo Nagaoka

  DOI：10.3987/com-18-s(t)82

  日期：——

  A selective and efficient synthesis of t-butyl 3-alkyl-N-hydroxy-oxindole-3-carboxylates from di-t-butyl 2-nitrophenylmalonates is described. A tandem reduction-cyclization approach involving reduction of di-t-butyl 2-methyl-(2-nitrophenyl)malonate to di-t-butyl 2-(2-(hydroxyamino)phenyl)-2-methylmalonate followed by accelerated cyclization reaction using a combination of Rh/C and hydrazine monohydrate smoothly and selectively afforded the N-hydroxy-oxindole scaffold. This methodology was successfully applied to gram-scale-synthesis of the t-butyl N-hydroxy-3-methyl-oxindole-3-carboxylate 1 without silica gel column chromatographic separation step.