(R)-(5-bromo-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester | 370861-58-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (R)-(5-bromo-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester
• 英文别名: (R)-(5-bromo-indan-2-yl)-carbamic acid methyl ester；(R)-(5-bromoindan 2-yl)-carbamic acid methyl ester；methyl N-[(2R)-5-bromo-2,3-dihydro-1H-inden-2-yl]carbamate
• CAS: 370861-58-8
• 化学式: C₁₁H₁₂BrNO₂
• 分子量: 270.126
• InChiKey: JQSPJJDBVKBXGC-SNVBAGLBSA-N

物化性质

• 沸点：
  372.9±42.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-(5-bromo-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester 在 tris-(dibenzylideneacetone)dipalladium(0) 盐酸 、 sodium methylate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 反应 17.5h， 生成 (R)-(5-amino-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester
  参考文献：
  名称：

  Efficient and Practical Syntheses of ( R )‐(5‐Amino‐2,3‐dihydro‐1 H ‐inden‐2‐yl)‐carbamic Acid Methyl Ester

  摘要：

  DOI：

  10.1002/1615-4169(200107)343:5<461::aid-adsc461>3.0.co;2-#
• 作为产物：
  描述：

  2-氨基茚满盐酸盐 在 溴 、 碳酸氢钠 作用下， 以 醋酸异丙酯 、 水 为溶剂， 反应 1.0h， 生成 (R)-(5-bromo-2,3-dihydro-1H-inden-2-yl)carbamic acid methyl ester
  参考文献：
  名称：

  Efficient and Practical Syntheses of ( R )‐(5‐Amino‐2,3‐dihydro‐1 H ‐inden‐2‐yl)‐carbamic Acid Methyl Ester

  摘要：

  DOI：

  10.1002/1615-4169(200107)343:5<461::aid-adsc461>3.0.co;2-#

文献信息

• Carboxamides useful as inhinitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion
  申请人：——

  公开号：US20030109700A1

  公开（公告）日：2003-06-12

  1 Compounds of formula (1) wherein R 2 —C, R 3 —C, R 4 —C or R 5 —C may be replaced by N; and wherein n is 1, 2 or 3; R 1 is aryl, heteroaryl or (aryl or heteroaryl)-lower alkoxy; R 2 , R 3 , R 4 and R 5 are independently hydrogen, lower alkyl, lower alkoxy, halo, trifluoromethyl or cyano; R 6 is (i) or (ii) m is 1, 2 or 3; R 7 is hydrogen, lower alkyl (aryl or heteroaryl)-lower alkyl, lower alkoxy, (aryl or heteroaryl)-lower alkoxy, hydroxy, oxo, lower alkylenedioxy or lower alkanoyloxy; W is O, S or NR 8 ; R 8 is —COR a , (iii), —COOR d , —SO 2 R e , hydrogen, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R a , R d and R e , are independently optionally substituted lower alkyl, cycloalkyl, adamantyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R b and R c are independently hydrogen, cycloalkyl, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl) lower alkyl; or R b and R c together represent lower alkylene; and pharmaceutically acceptable salts thereof; and enantiomers thereof; which are useful as inhibitors of microsomal triglyceride transfer protein (MTP) and of apolipoprotein B (apoB) secretion.

  式（1）的化合物中，其中R2—C，R3—C，R4—C或R5—C可以被N取代；其中n为1、2或3；R1为芳基，杂环芳基或（芳基或杂环芳基）-较低烷氧基；R2、R3、R4和R5独立地为氢、较低烷基、较低烷氧基、卤素、三氟甲基或氰基；R6为（i）或（ii）m为1、2或3；R7为氢、较低烷基（芳基或杂环芳基）-较低烷基、较低烷氧基、（芳基或杂环芳基）-较低烷氧基、羟基、氧代、较低烷二氧基或较低烷酰氧基；W为O、S或NR8；R8为—CORa、（iii）、—COORd、—SO2Re、氢、可选择取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基；Ra、Rd和Re独立地为可选择取代的较低烷基、环烷基、脱氢脂肪基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基；Rb和Rc独立地为氢、环烷基、可选择取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）较低烷基；或Rb和Rc一起代表较低烷基；以及其药学上可接受的盐；以及其对映体；它们可用作微粒体三酰甘油转移蛋白（MTP）和载脂蛋白B（apoB）分泌的抑制剂。
• Amino-benzocycloalkane derivatives
  申请人：Novartis AG

  公开号：US06197798B1

  公开（公告）日：2001-03-06

  Compounds of the formula I wherein R2—C, R3—C, R4—C or R5—C may be replaced by N; and wherein n is 1, 2 or 3; R1 is aryl, cycloalkyl or heterocyclyl; R2, R3, R4 and R5 are independently hydrogen, optionally substituted alkyl, halo, amino, substituted amino, trifluoromethyl, cyano, carboxyl, alkoxycarbonyl, aralkoxycarbonyl, (alkyl, aryl or aralkyl)-thio, (alkyl, aryl or aralkyl)-oxy, acyloxy, (alkyl, aryl or aralkyl)-aminocarbonyloxy; or any two of R2, R3, R4 and R5 at adjacent positions are alkylenedioxy; R6 is hydrogen, optionally substituted alkyl, amino, substituted amino, acylamino, wherein Ra is hydrogen or optionally substituted alkyl, Rb and Rc are independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; or Rb and Rc together represent lower alkylene or lower alkylene interrupted by O, S, or N—(H, alkyl or aralkyl); Rd is optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; and Re is optionally substituted alkyl, aryl, heterocyclyl, cycloalkyl, amino or substituted amino; and pharmaceutically acceptable salts thereof; and enantiomers thereof; which are useful as inhibitors of microsomal triglyceride transfer protein (MTP) and of apolipoprotein B (ApoB) secretion.

  根据您的要求，以下是公式I化合物的中文翻译： 化合物具有公式I，其中R2—C、R3—C、R4—C或R5—C可以被N取代；并且其中n为1、2或3；R1为芳基、环烷基或杂环基；R2、R3、R4和R5独立地为氢、可选地取代的烷基、卤素、氨基、取代氨基、三氟甲基、氰基、羧基、烷氧羰基、芳烷氧羰基、(烷基、芳基或芳烷基)硫基、(烷基、芳基或芳烷基)氧基、酰氧基、(烷基、芳基或芳烷基)氨基甲氧基；或者R2、R3、R4和R5中任意两个相邻位置的为烷基亚甲基二氧基；R6为氢、可选地取代的烷基、氨基、取代氨基、酰氨基，其中Ra为氢或可选地取代的烷基，Rb和Rc独立地为氢、可选地取代的烷基、环烷基、芳基或杂环基；或者Rb和Rc共同代表低碳烯基或由O、S或N—(H、烷基或芳烷基)打断的低碳烯基；Rd为可选地取代的烷基、环烷基、芳基或杂环基；Re为可选地取代的烷基、芳基、杂环基、环烷基、氨基或取代氨基；以及药用可接受的盐；以及它们的对映体；这些化合物可用作微粒体甘油三酯转移蛋白（MTP）和载脂蛋白B（ApoB）分泌的抑制剂。
• Process Research and Development of a MTP Inhibitor: Another Case of Disappearing Polymorphs upon Scale-up
  作者：Mahavir Prashad、Paul Sutton、Raeann Wu、Bin Hu、James Vivelo、Joseph Carosi、Prasad Kapa、Jessica Liang

  DOI：10.1021/op100115u

  日期：2010.7.16

  Knowledge of the molecule’s polymorphic nature prompted extensive polymorphic screening using drug substance produced by the earlier synthesis routes. These studies revealed the existence of a third polymorph, Form C. Subsequently, Form C was selected for further development based on data from the additional formulation and polymorphic studies. Surprisingly, a new modification, Form D, appeared when the

  LAB687是微粒体甘油三酸酯转移蛋白（MTP）的抑制剂，旨在降低甘油三酸酯和LDL胆固醇。其多晶型形式的发现与分子的合成发展紧密相关。在开发的早期阶段，已知LAB687会以两种修饰形式晶型A和B结晶。对分子多态性的了解促使人们使用较早合成途径生产的药物进行了广泛的多态性筛选。这些研究表明存在第三种多晶型物C型。随后，根据来自其他配方和多晶型研究的数据，选择了C型进行进一步开发。令人惊讶的是，在中试工厂扩大了常规生产C型结晶的结晶工艺时，出现了一种新的修饰形式D型。一旦将表格D引入实验室，就无法再制作表格A和C。我们假设由于合成的变化而引起的药物杂质分布的变化导致了最稳定的形式D的出现。
• Carboxamides useful as inhibitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion
  申请人：Ksander Gary Michael

  公开号：US06878707B2

  公开（公告）日：2005-04-12

  Compounds of formula (I) wherein R 2 —C, R 3 —C, R 4 —C or R 5 —C may be replaced by N; and wherein n is 1, 2 or 3; R 1 is aryl, heteroaryl or (aryl or heteroaryl)-lower alkoxy; R 2 , R 3 , R 4 and R 5 are independently hydrogen, lower alkyl, lower alkoxy, halo, trifluoromethyl or cyano; R 6 is (i) or (ii) m is 1, 2 or 3; R 7 is hydrogen, lower alkyl (aryl or heteroaryl)-lower alkyl, lower alkoxy, (aryl or heteroaryl)-lower alkoxy, hydroxy, oxo, lower alkylenedioxy or lower alkanoyloxy; W is O, S or NR 8 ; R 8 is —COR a , (iii), —COOR d , —SO 2 R e , hydrogen, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R a , R d and R e are independently optionally substituted lower alkyl, cycloalkyl, adamantyl, aryl, heteroaryl or (aryl or heteroaryl)-lower alkyl; R b and R c are independently hydrogen, cycloalkyl, optionally substituted lower alkyl, aryl, heteroaryl or (aryl or heteroaryl) lower alkyl; or R b and R c together represent lower alkylene; and pharmaceutically acceptable salts thereof; and enantiomers thereof; which are useful as inhibitors of microsomal triglyceride transfer protein (MTP) and of apolipoprotein B (apoB) secretion.

  化合物的公式（I），其中R2-C，R3-C，R4-C或R5-C可以被N替换;其中n为1、2或3; R1为芳基、杂环芳基或（芳基或杂环芳基）-较低烷氧基; R2、R3、R4和R5独立地为氢、较低烷基、较低烷氧基、卤素、三氟甲基或氰基; R6为（i）或（ii），m为1、2或3; R7为氢、较低烷基（芳基或杂环芳基）-较低烷基、较低烷氧基、（芳基或杂环芳基）-较低烷氧基、羟基、氧代、较低烷二氧基或较低烷酰氧基; W为O、S或NR8; R8为-CORa、（iii）、-COORd、-SO2Re、氢、可选择性取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基; Ra、Rd和Re独立地为可选择性取代的较低烷基、环烷基、金刚烷基、芳基、杂环芳基或（芳基或杂环芳基）-较低烷基; Rb和Rc独立地为氢、环烷基、可选择性取代的较低烷基、芳基、杂环芳基或（芳基或杂环芳基）较低烷基;或Rb和Rc共同代表较低烷基;以及其药学上可接受的盐;和其对映异构体;这些化合物可用作微粒体甘油三酯转移蛋白（MTP）和载脂蛋白B（apoB）分泌的抑制剂。
• CARBOXAMIDES USEFUL AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND OF APOLIPOPROTEIN B SECRETION
  申请人：Novartis AG

  公开号：EP1259484B1

  公开（公告）日：2005-05-18