(2S)-4-苄基吗啉-2-羧酸 | 1030837-49-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: (2S)-4-苄基吗啉-2-羧酸
• 中文别名: (S)-4-苄基吗啉-2-羧酸
• 英文名称: (S)-4-benzyl-morpholine-2-carboxylic acid
• 英文别名: (S)-4-benzylmorpholine-2-carboxy ester；(2S)-4-benzylmorpholin-4-ium-2-carboxylate
• CAS: 1030837-49-0
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: UJDWIUOGWSDEFP-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-4-苄基吗啉-2-羧酸 在 氢气 、 palladium(II) hydroxide 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium bromide 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~120.0 ℃ 、300.01 kPa 条件下， 反应 108.0h， 生成
  参考文献：
  名称：

  [EN] PURINE DERIVATIVES, AS NR2B NEGATIVE MODULATORS AND THE USE THEREOF AS MEDICAMENT, IN PARTICULAR FOR TREATING DEPRESSIVE DISORDERS
  [FR] DÉRIVÉS DE PURINE, UTILISÉS EN TANT QUE MODULATEURS NÉGATIFS DE NR2B ET LEUR UTILISATION EN TANT QUE MÉDICAMENT, EN PARTICULIER POUR LE TRAITEMENT DE TROUBLES DÉPRESSIFS

  摘要：

  本发明涉及一般式A的新型嘌呤化合物，以及它们的制备方法、含有它们的药物组合物以及它们在治疗中的应用，特别是在与NR2B负性变构调节性质相关的疾病的治疗或预防中的应用。

  公开号：

  WO2020245136A1
• 作为产物：
  描述：

  N-苄基乙醇胺 在 盐酸 、 硫酸 、 Methyl Tertiary-Butyl Ether Water 作用下， 以 水 、 甲苯 为溶剂， 反应 39.33h， 生成 (2S)-4-苄基吗啉-2-羧酸
  参考文献：
  名称：

  [EN] A COMPOUND FOR INHIBITING HUMAN 11-ß-HYDROXY STEROID DEHYDROGENASE TYPE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] COMPOSÉ CAPABLE D'INHIBER LA 11-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1 HUMAINE ET COMPOSITION PHARMACEUTIQUE EN CONTENANT

  摘要：

  公开号：

  WO2012128582A3

文献信息

• Design and synthesis of morpholine derivatives. SAR for dual serotonin & noradrenaline reuptake inhibition
  作者：Paul V. Fish、Christopher Deur、Xinmin Gan、Keri Greene、David Hoople、Malcolm Mackenny、Kimberly S. Para、Keith Reeves、Thomas Ryckmans、Cory Stiff、Alan Stobie、Florian Wakenhut、Gavin A. Whitlock

  DOI：10.1016/j.bmcl.2008.03.050

  日期：2008.4

  Single enantiomer (SS) and (RR) 2-[(phenoxy)(phenyl)methyl]morpholine derivatives 5, 8-23 are inhibitors of monoamine reuptake. Target compounds were prepared using an enantioselective synthesis employing a highly specific enzyme-catalysed resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (26) as the key step. Structure-activity relationships established that serotonin and noradrenaline

  单一对映异构体（SS）和（RR）2-[（（苯氧基）（苯基）甲基]吗啉衍生物5、8-23是单胺再摄取的抑制剂。使用对映体选择性合成方法制备目标化合物，该方法采用高特异性酶催化的外消旋4-苄基吗啉-2-羧酸正丁酯（26）作为关键步骤。建立了构效关系，认为5-羟色胺和去甲肾上腺素的再摄取抑制是立体化学和芳基/芳氧基取代的功能。因此，所有选择性SRI，选择性NRI和双重SNRI均已确定。选择其中一种化合物，即强效和选择性双重SNRI（SS）-5a作为进一步临床前评估的候选药物。
• Enantioselective synthesis of (R)- and (S)-N-Boc-morpholine-2-carboxylic acids by enzyme-catalyzed kinetic resolution: application to the synthesis of reboxetine analogs
  作者：Paul V. Fish、Malcolm Mackenny、Gerwyn Bish、Timothy Buxton、Russell Cave、David Drouard、David Hoople、Alan Jessiman、Duncan Miller、Christelle Pasquinet、Bhairavi Patel、Keith Reeves、Thomas Ryckmans、Melanie Skerten、Florian Wakenhut

  DOI：10.1016/j.tetlet.2008.11.025

  日期：2009.1

  The (R)- and (S)-N-Boc-morpholine-2-carboxylic acids 9 and 10 were prepared using an enantioselective synthesis employing a highly selective enzyme-catalyzed kinetic resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (11) as the key step. Acids 9 and 10 were then converted efficiently and stereoselectively to reboxetine analogs 3 and 4.

  （R）-和（S）-N -Boc-吗啉-2-羧酸9和10是使用对映选择性合成方法制备的，该合成方法是使用高选择性酶催化的外消旋4-苄基吗啉-2-羧酸正丁酯进行动力学拆分（11）作为关键步骤。然后将酸9和10有效和立体选择性地转化为瑞波西汀类似物3和4。
• Morpholine Carboxamide Prokineticin Receptor Antagonists
  申请人：Thompson Wayne J.

  公开号：US20090306076A1

  公开（公告）日：2009-12-10

  The present invention is directed to morpholine carboxamide compounds which are antagonists of prokineticin receptors, in particular antagonists of prokineticin 2 receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which prokineticin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which prokineticin receptors are involved.

  本发明涉及形态啉羧酰胺化合物，其为促动素受体拮抗剂，特别是促动素2受体拮抗剂，可用于治疗或预防神经和精神障碍和疾病，其中涉及促动素受体。本发明还涉及包含这些化合物的制药组合物以及在涉及促动素受体的这种疾病的预防或治疗中使用这些化合物和组合物的用途。
• Purine derivatives and the use thereof as medicament
  申请人：Boehringer Ingelheim International GmbH

  公开号：US11376258B2

  公开（公告）日：2022-07-05

  The present invention relates to novel purines of general formula A processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment or prevention of conditions having an association with NR2B negative allosteric modulating properties.

  本发明涉及通式 A 的新型嘌呤 的制备工艺、含有它们的药物组合物以及它们在治疗中的用途，特别是在治疗或预防与 NR2B 负异位调节特性有关的疾病中的用途。
• Practical Asymmetric Synthesis of an Edivoxetine·HCl Intermediate via an Efficient Diazotization Process
  作者：Michael E. Kopach、Perry C. Heath、Roger B. Scherer、Mark A. Pietz、Bret A. Astleford、Mary Kay McCauley、Utpal K Singh、Sze Wing Wong、David M. Coppert、Mark S. Kerr、Peter G. Houghton、Gary A. Rhodes、Gregg A. Tharp

  DOI：10.1021/acs.oprd.5b00014

  日期：2015.4.17

  A convergent synthesis of (S)-(4-benzylmorpholin-2-yl)(morpholino)methanone methanesulfonate (1), a key regulatory starting material for edivoxetine HCl, was developed at Eli Lilly & Company. This novel synthesis utilizes d-serine as the source of chirality, which is preserved throughout the synthesis. Key features include the development of a scalable diazotization process to produce (S)-epoxy acid 7, which was optimized to improve the process safety profile. The final (S)-morpholino acid intermediate 11 was converted to the title compound using T3P with >99.9% purity in 75% yield. Life cycle analysis of the new route revealed a 69% reduction in global warming potential (GWP) for solvent usage relative to the prior route of manufacture.