(2R,3S)-4-benzyl-2-({1-[3,5-bis(trifluoromethyl)phenyl]-vinyl}oxy)-3-(4-fluorophenyl)morpholine | 170729-77-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (2R,3S)-4-benzyl-2-({1-[3,5-bis(trifluoromethyl)phenyl]-vinyl}oxy)-3-(4-fluorophenyl)morpholine
• 英文别名: (2R,3S)-3-(4-fluorophenyl)-4-(phenylmethyl)-2-morpholinyl 3,5-bis(fluoromethyl)benzoic acid；(2R,3S)-3-(4-fluorophenyl)-4-benzyl-2-morpholinyl 3,5-bis(trifluoromethyl)benzoate；2-(R)-(3,5-bis(trifluoromethyl)benzoyloxy)-3-(S)-(4-fluoro)-phenyl-4-benzyl-morpholine；2-(R)-(3,5-Bis(trifluoromethyl)benzoyloxy)-3-(S)-(4-fluoro)phenyl-4-benzyl morpholine；2-(R)-(3,5-bis(trifluoromethyl)benzoyloxy)-3-(S)-(4-fluoro)phenyl-4-benzyl-morpholine；(2R,3S)-(4-benzyl-3-(4-fluorophenyl)morpholin-2-yl)-3,5-bis(trifluoromethyl)benzoate；(2R,3S)-4-Benzyl-3-(4-fluorophenyl)-2-morpholinyl 3,5-bis(trifluoromethyl)benzoate；[(2R,3S)-4-benzyl-3-(4-fluorophenyl)morpholin-2-yl] 3,5-bis(trifluoromethyl)benzoate
• CAS: 170729-77-8
• 化学式: C₂₆H₂₀F₇NO₃
• 分子量: 527.439
• InChiKey: SGOLWTAOZHLBNT-LADGPHEKSA-N

物化性质

• 沸点：
  508.9±50.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2R,3S)-4-benzyl-2-({1-[3,5-bis(trifluoromethyl)phenyl]-vinyl}oxy)-3-(4-fluorophenyl)morpholine 以60%的产率得到(2R,3S)-2-[[1-[3,5-bis(trifluoromethyl)phenyl]ethenyl]oxy]-3-(4-fluorophenyl)-4-(phenylmethyl)morpholine
  参考文献：
  名称：

  Morpholine compounds are prodrugs useful as tachykinin receptor

  摘要：

  通用结构式##STR1##的替代杂环化合物是在治疗炎症性疾病、疼痛或偏头痛、哮喘和呕吐方面有用的催吐素受体拮抗剂。

  公开号：

  US05691336A1
• 作为产物：
  描述：

  3,5-双三氟甲基苯甲酰氯 在 L-Selectride 作用下， 以 四氢呋喃 为溶剂， 反应 3.83h， 生成 (2R,3S)-4-benzyl-2-({1-[3,5-bis(trifluoromethyl)phenyl]-vinyl}oxy)-3-(4-fluorophenyl)morpholine
  参考文献：
  名称：

  WO2008/26216

  摘要：

  公开号：

文献信息

• PROCESS FOR PURIFICATION OF APREPITANT
  申请人：Parthasaradhi Reddy Bandi

  公开号：US20090149462A1

  公开（公告）日：2009-06-11

  The present invention relates to a process for obtaining pure aprepitant substantially free of undesired diastereomeric isomer, namely 5-[2(S)-[1(RS)-[3,5-bis(trifluoromethyl)-phenyl)ethoxy]-3-(S)-(4-fluorophenyl)-morpholin-4-yl-methyl]-3,4-dihydro-2H-1,2,4-triazol-3-one. The present invention further provides an improved process for preparation of aprepitant crystalline form II. The present invention also relates to novel amorphous form of aprepitant, a process for its preparation and to a pharmaceutical composition comprising it. The present invention further relates to aprepitant having a mean particle size of less than about 11.5 microns, a process for its preparation and to a pharmaceutical composition comprising it. Thus, for example, aprepitant having a content of diastereomeric impurity of 1.1% is dissolved in ethyl acetate at 70° C., the solution is concentrated to half the initial volume by distilling off ethyl acetate, and the resulting solid is collected at 0-5° C. to give pure aprepitant substantially free of its diastereomeric impurity.

  本发明涉及一种几乎不含不需要的立体异构体，即5-[2(S)-[1(RS)-[3,5-双(三氟甲基)苯基)乙氧基]-3-(S)-(4-氟苯基)吗啉-4-基甲基]-3,4-二氢-2H-1,2,4-三唑-3-酮的纯阿瑞吡坦的制备工艺。本发明进一步提供了一种改进的制备阿瑞吡坦II型结晶形式的方法。本发明还涉及一种新的阿瑞吡坦无定形形式、其制备方法以及包含该无定形形式的药物组合物。本发明还涉及平均粒径小于约11.5微米的阿瑞吡坦、其制备方法以及包含它的药物组合物。因此，例如，含有1.1%立体异构体杂质的阿瑞吡坦在70°C下溶于乙酸乙酯中，通过蒸馏掉乙酸乙酯将溶液浓缩到初始体积的一半，然后在0-5°C下收集所得固体，以得到几乎不含其立体异构体杂质的纯阿瑞吡坦。
• [¹⁴C]Dimethyltitanocene and [¹⁴C]Methyl(methyltrimethylsilyl) titanocene-Reagents for the [¹⁴C]olefination of carbonyl compounds: synthesis of [¹⁴C]Aprepitant
  作者：M. A. Wallace、D. C. Dean、D. G. Melillo

  DOI：10.1002/jlcr.1667

  日期：2009.9.30

  A neurokinin (NK-1) receptor antagonist, [14C]Aprepitant, was synthesized using two labeled olefination reagents: [14C]dimethyltitanocene 1 and [14C]methyl (methyltrimethylsilyl)titanocene 7. Both reagents can be readily prepared from [14C]methyllithium and have been shown to convert a variety of carbonyls to [14C]methylenes in good radiochemical yields. Copyright © 2009 John Wiley & Sons, Ltd.

  神经激肽 (NK-1) 受体拮抗剂 [14C]Aprepitant 是使用两种标记的烯化试剂合成的：[14C]二甲基二茂钛 1 和 [14C] 甲基（甲基三甲基甲硅烷基）二茂钛 7。这两种试剂都可以从 [14C] 甲基锂轻松制备并且已被证明可以以良好的放射化学产率将各种羰基转化为 [14C] 亚甲基。版权所有 © 2009 John Wiley & Sons, Ltd.
• Morpholine and thiomorpholine tachykinin receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05872116A1

  公开（公告）日：1999-02-16

  Substituted heterocycles of the general structural formula: ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.

  通用结构式的替代杂环化合物：##STR1## 是在治疗炎症性疾病、疼痛或偏头痛、哮喘和呕吐方面有用的速激肽受体拮抗剂，以及在治疗心血管疾病如心绞痛、高血压或缺血方面有用的钙通道阻滞剂。
• Treatment of emesis with morpholine tachykinin receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05512570A1

  公开（公告）日：1996-04-30

  Substituted heterocycles of the structural formula: ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma, emesis and nausea.

  结构式的替代杂环化合物：##STR1## 是在治疗炎症性疾病、疼痛或偏头痛、哮喘、呕吐和恶心中有用的速激肽受体拮抗剂。
• Process for preparing morpholine tachykinin receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05637699A1

  公开（公告）日：1997-06-10

  Substituted heterocycles of the general structural formula: ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.

  通用结构式为：##STR1## 的替代杂环化合物是在治疗炎症性疾病、疼痛或偏头痛、哮喘和呕吐方面有用的催吐史肽受体拮抗剂，以及在治疗心血管疾病如心绞痛、高血压或缺血方面有用的钙通道阻滞剂。