N-(3,4-dichlorobenzyl)-2(R)-(phthalimidomethyl)morpholine | 610305-43-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-(3,4-dichlorobenzyl)-2(R)-(phthalimidomethyl)morpholine
• 英文别名: 2-{[(2R)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}-1H-isoindole-1,3-(2H)-dione；2-[4-(3,4-dichloro-benzyl)-morpholin-2-ylmethyl]-isoindole-1,3-dione；2-[[(2R)-4-[(3,4-Dichlorophenyl)methyl]morpholin-2-yl]methyl]isoindoline-1,3-dione；2-[[(2R)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]isoindole-1,3-dione
• CAS: 610305-43-6
• 化学式: C₂₀H₁₈Cl₂N₂O₃
• 分子量: 405.281
• InChiKey: GYQBANNDJUCMNR-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  N-(3,4-dichlorobenzyl)-2(R)-(phthalimidomethyl)morpholine 在 potassium hydroxide 、 肼 作用下， 以 乙醇 、 甲基叔丁基醚 、 水 、 甲苯 为溶剂， 反应 1.93h， 生成 (2S)-N-{[4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}chloroacetamide
  参考文献：
  名称：

  THERAPEUTIC AGENT FOR OPHTHALMIC DISEASE

  摘要：

  本发明提供一种治疗或预防由眼部血管生成引起的眼科疾病的治疗剂或预防剂，其含有由式（1）所代表的吗啉化合物，其中环A是芳基，可选择地具有取代基等；环B是芳基，可选择地具有取代基等；m=0-2；n=1-5；X是键等；Y是键等；Z是氢原子等，或其药学上可接受的盐作为活性成分。

  公开号：

  US20160193217A1
• 作为产物：
  描述：

  2-(3,4-二氯苄氨基)-乙醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 丙醇 、 甲苯 为溶剂， 反应 5.0h， 生成 N-(3,4-dichlorobenzyl)-2(R)-(phthalimidomethyl)morpholine
  参考文献：
  名称：

  A Mitsunobu Diol Cyclisation to Chiral Morpholines and Dioxanes

  摘要：

  介绍了在 Mitsunobu 条件下进行的二元醇环化反应，通过这种反应可以获得手性取代的吗啉和二氧杂环烷。

  DOI：

  10.1055/s-2006-948184

文献信息

• [EN] PROCESS FOR THE PREPARATION OF MORPHOLINE DERIVATIVES AND INTERMEDIATES THEREFORE<br/>[FR] PROCEDE DE PREPARATION DE DERIVES DE MORPHOLINE ET PRODUITS INTERMEDIAIRES OBTENUS A CET EFFET
  申请人：GLAXO GROUP LTD

  公开号：WO2003082835A1

  公开（公告）日：2003-10-09

  Processes for the preparation of a compound of formula (IIIA)(I), or a salt thereof; wherein; Z represents a bond, CO, SO2, CR10R7(CH2)n, (CH2)nCR10R7, CHR7(CH2)nO, CHR7(CH2)nS, CHR7(CH2)nOCO, CHR7(CH2)nCO, COCHR7(CH2)n or SO2CHR7(CH2)n; R6 represents C1-6 alkyl, C2-6 alkenyl, aryl, heteroaryl, aryl-C2-6 alkenyl-, -CN or a group of formula -Y2-J3; R7 represents hydrogen, C1-4 alkyl, CONR8R9 or COOC1-6 alkyl;a and b represent 1 or 2, such that a+b represents 2 or 3;n represents an integer from 0 to 4; M represents a C3-8 cycloalkyl or C3-8 cycloalkenyl group fused to a monocyclic aryl or monocyclic heteroaryl group; J3 represents a moiety of formula (K): (II), wherein X1 represents oxygen, NR11 or sulphur, X2 represents CH2, oxygen, NR12 or sulphur, m1 represents an integer from 1 to 3 and m2 represents an integer from 1 to 3, provided that m1+m2 is in the range from 3 to 5, also provided that when both X1 and X2 represent oxygen, NR11, NR12 or sulphur, m1 and m2 must both not equal less than 2, wherein (K) is optionally substituted by one or more (eg. 1 or 2) -Y3-aryl, -Y3-heteroaryl, -Y3-CO-aryl, -COC3-8 cycloalkyl, -Y3-CO-heteroaryl, -C1-6 alkyl, -Y3-COOC1-6 alkyl, -Y3-COC1-6 alkyl, -Y3-W, -Y3-CO-W, -Y3-NR15R16, -Y3-CONR15R16, hydroxy, oxo, -Y3-SO2NR15R16, -Y3-SO2C1-6 alkyl, -Y3-SO2aryl, -Y3-SO2heteroaryl, -Y3-NR13C1-6 alkyl, -Y3-NR13SO2C1-6 alkyl, -Y3-NR13CONR15R16, -Y3-NR13COOR14 or -Y3-OCONR15R16 groups, and is optionally fused to a monocyclic aryl or heteroaryl ring; R8, R9, R10, R11, R12, R13 and R14 independently represent hydrogen or C1-6 alkyl; R15 and R16 independently represent hydrogen or C1-6 alkyl or R15 and R16 together with the nitrogen atom to which they are attached may form a morpholine, piperidine or pyrrolidine ring; R17 and R18 independently represent hydrogen or C1-6 alkyl; W represents a saturated or unsaturated, non-aromatic 5-7 membered ring containing between 1 and 3 heteroatoms selected from nitrogen, oxygen or sulphur, optionally substituted with one or more C1-6 alkyl, halogen or hydroxy groups; Y1, Y2 and Y3 independently represent a bond or a group of formula -(CH2)pCRcRd(CH2)q- wherein Rc and Rd independently represent hydrogen or C1-4 alkyl or Rc and Rd may together with the carbon atom to which they are attached form a C3-8 cycloalkyl group, and p and q independently represent an integer from 0 to 5 wherein p + q is an integer from 0 to 5;, and; k is 1 or 2;are disclosed.

  关于制备化合物的方法，该化合物的化学式为(IIIA)(I)，或其盐；其中；Z代表一个键，CO，SO2，CR10R7(CH2)n，(CH2)nCR10R7，CHR7(CH2)nO，CHR7(CH2)nS，CHR7(CH2)nOCO，CHR7(CH2)nCO，COCHR7(CH2)n或SO2CHR7(CH2)n；R6代表C1-6烷基，C2-6烯基，芳基，杂环芳基，芳基-C2-6烯基，-CN或一个化学式为-Y2-J3的基团；R7代表氢，C1-4烷基，CONR8R9或COOC1-6烷基；a和b代表1或2，使得a+b代表2或3；n代表0到4之间的整数；M代表与一个单环芳基或单环杂环芳基融合的C3-8环烷基或C3-8环烯基基团；J3代表一个化学式(K)的基团：(II)，其中X1代表氧，NR11或硫，X2代表CH2，氧，NR12或硫，m1代表1到3之间的整数，m2代表1到3之间的整数，前提是m1+m2在3到5的范围内，同时当X1和X2都代表氧，NR11，NR12或硫时，m1和m2都不能小于2；其中(K)可以选择地被一个或多个(例如1或2个) -Y3-芳基，-Y3-杂环芳基，-Y3-CO-芳基，-COC3-8环烷基，-Y3-CO-杂环芳基，-C1-6烷基，-Y3-COOC1-6烷基，-Y3-COC1-6烷基，-Y3-W，-Y3-CO-W，-Y3-NR15R16，-Y3-CONR15R16，羟基，酮基，-Y3-SO2NR15R16，-Y3-SO2C1-6烷基，-Y3-SO2芳基，-Y3-SO2杂环芳基，-Y3-NR13C1-6烷基，-Y3-NR13SO2C1-6烷基，-Y3-NR13CONR15R16，-Y3-NR13COOR14或-Y3-OCONR15R16基团取代，也可以选择地与一个单环芳基或杂环芳基环融合；R8、R9、R10、R11、R12、R13和R14独立地代表氢或C1-6烷基；R15和R16独立地代表氢或C1-6烷基，或者R15和R16与它们连接的氮原子一起可以形成吗啡啉、哌啶或吡咯烷环；R17和R18独立地代表氢或C1-6烷基；W代表一个饱和或不饱和的非芳香5-7环，含有1到3个从氮、氧或硫中选择的杂原子，可以选择地取代一个或多个C1-6烷基、卤素或羟基；Y1、Y2和Y3独立地代表一个键或一个化学式-(CH2)pCRcRd(CH2)q-，其中Rc和Rd独立地代表氢或C1-4烷基，或者Rc和Rd可以与它们连接的碳原子一起形成一个C3-8环烷基，p和q独立地代表0到5之间的整数，其中p+q是0到5之间的整数；k为1或2；以上所述。
• Benzenesulphonate salt of a morpholine urea derivative for use as a ccr-3 antagonist in the treatment of inflammatory conditions
  申请人：Cook Spencer John

  公开号：US20060089497A1

  公开（公告）日：2006-04-27

  Compounds of formula (I): wherein A − represents the benzenesulphonate (besylate) anion; R represents H or C 1-6 alkyl; and n is a number from 0.8 to 2.2 are CCR3 antagonists and are therefore indictated to be useful in therapy are described.

  式(I)的化合物：其中A-代表苯磺酸根（苯磺酸盐）阴离子；R代表H或C1-6烷基；n是从0.8到2.2的数字，是CCR3拮抗剂，因此适用于治疗。
• Benzenesulphonate salt of a morpholine urea derivative for use as a CCR-3 antagonist in the treatment of inflammatory conditions
  申请人：Glaxo Group Limited

  公开号：US07531651B2

  公开（公告）日：2009-05-12

  Compounds of formula (I): wherein A− represents the benzenesulphonate (besylate) anion;. R represents H or C1-6 alkyl; and n is a number from 0.8 to 2.2 are CCR3 antagonists and are therefore indicated to be useful in therapy are described.

  公式（I）的化合物：其中A-代表苯磺酸盐（besylate）阴离子；R代表H或C1-6烷基；n是从0.8到2.2的数字，是CCR3拮抗剂，因此被指示用于治疗。
• Therapeutic agent for ophthalmic disease
  申请人：MITSUBISHI TANABE PHARMA CORPORATION

  公开号：US10130634B2

  公开（公告）日：2018-11-20

  The present invention provides a therapeutic agent or prophylactic agent for an ophthalmic disease caused by ocular angiogenesis, which contains a morpholine compound represented by the formula (1) wherein ring A is aryl optionally having substituent(s) and the like; ring B is arylene optionally having substituent(s) and the like; m=0-2; n=1-5; X is a bond and the like; Y is a bond and the like; and Z is a hydrogen atom and the like, or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明提供了一种由眼部血管生成引起的眼科疾病的治疗剂或预防剂，它含有由式（1）表示的吗啉化合物 其中，环 A 是芳基，可选具有取代基等；环 B 是芳烯，可选具有取代基等；m=0-2；n=1-5；X 是键等；Y 是键等；Z 是氢原子等，或其作为活性成分的药学上可接受的盐。
• [EN] MORPHOLINE DERIVATIVES AND INTERMEDIATES THEREFOR<br/>[FR] NOUVEAU COMPOSE
  申请人：——

  公开号：WO2003082834A3

  公开（公告）日：2004-03-25