tert-butyl methyl(2-morpholino-2-oxoethyl)carbamate | 124072-76-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl methyl(2-morpholino-2-oxoethyl)carbamate
• 英文别名: tert-butyl N-methyl-N-(2-morpholin-4-yl-2-oxoethyl)carbamate
• CAS: 124072-76-0
• 化学式: C₁₂H₂₂N₂O₄
• 分子量: 258.318
• InChiKey: QZRWPFZTDCFKJD-UHFFFAOYSA-N

物化性质

• 沸点：
  387.5±42.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl methyl(2-morpholino-2-oxoethyl)carbamate 、 5-溴-2-氟三氟甲苯 在 异丙基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 5.17h， 生成
  参考文献：
  名称：

  Rapid Development and Scale-Up of a 1H-4-Substituted Imidazole Intermediate Enabled by Chemistry in Continuous Plug Flow Reactors

  摘要：

  The development of reactions in a continuous fashion in plug flow tube reactors (PFR) offers unique advantages to the drug development and scale-up process and can also enable chemistry that would be difficult to perform via batch processing. Herein, we report the development of two different continuous flow approaches to a key 1H-4-substituted imidazole intermediate (5). In a first generation approach, rapid optimization and scale-up of a challenging cyclization reaction was demonstrated in a PFR under GMP conditions to afford 29 kg of protected product 2. This material was further processed in batch equipment to deliver di-HCl salt 4. This first generation approach highlights the rapid development of chemistry in research-scale PFRs and speed to material delivery through linear scale up to a pilot-scale PFR under GMP conditions. In a second generation effort, a more efficient synthetic route was developed, and PFRs with automated sampling, dilution, and analytical analysis allowed for rapid and data-rich reaction optimization of both a key cyclization reaction and thermal removal of a Boc protecting group. This work culminated in 1 kg demonstration runs in a 0.22 L PFR for both continuous steps and shows the potential of commercialization from a lab hood footprint (1-2 MT/year).

  DOI：

  10.1021/op200351g
• 作为产物：
  描述：

  吗啉 、 叔丁氧羰酰基肌氨酸 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以32%的产率得到tert-butyl methyl(2-morpholino-2-oxoethyl)carbamate
  参考文献：
  名称：

  COMPOUNDS USEFUL AS MODULATORS OF TRPM8

  摘要：

  本发明包括作为TRPM8调节剂有用的化合物，例如式(Ia)、(Ib)和(Ic)的化合物，以及其亚属和种类；含有这些化合物的个人产品；以及利用这些化合物和个人产品，特别是利用增加或诱导化学感觉，如凉爽或冷感觉。

  公开号：

  US20150376136A1

文献信息

• New amino acid derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0300189A2

  公开（公告）日：1989-01-25

  A compound of the formula : wherein R1 is lower alkyl optionally substituted with a substituent selected from the group consisting of acyl,hydroxy, lower alkoxy, aryl, lower alkylthio and a group of the formula : in which R5 is hydrogen or acyl and R6 is hydrogen or lower alkyl; aryl; or amino optionally substituted with substituent(s) selected from the group consisting of lower alkyl and acyl; and R2 is hydrogen or lower alkyl; or R1 and R2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted with substituent(s) selected from the group consisting of lower alkyl, hydroxy(lower)alkyl, lower alkoxy(lower)alkyl, acyl(lower)alkyl, oxo and acyl; R3 is hydrogen or lower alkyl; and R4 is lower alkyl; and its pharmaceutically acceptable salt, processes for the preparation thereof and pharmaceutical composition comprising the same.

  一种式如下的化合物 其中 R1 是低级烷基，可任选被选自以下组别的取代基取代：酰基、羟基、低级烷氧基、芳基、低级烷硫基和一个式......的基团： 其中 R5 为氢或酰基，且 R6 是氢或低级烷基；芳基；或被选自低级烷基和酰基的取代基任选取代的氨基；以及 R2 是氢或低级烷基；或 R1 和 R2 与所连接的氮原子一起形成杂环基团，该杂环基团可任选被选自由低级烷基、羟基（低级）烷基、低级烷氧基（低级）烷基、酰基（低级）烷基、氧代和酰基组成的取代基取代； R3 是氢或低级烷基；和 R4 是低级烷基； 及其药学上可接受的盐、制备工艺和包含这些成分的药物组合物。
• Compounds useful as modulators of TRPM8
  申请人：Firmenich Incorporated

  公开号：US10421727B2

  公开（公告）日：2019-09-24

  The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.

  本发明包括可用作 TRPM8 调节剂的化合物，如式（Ia）、（Ib）和（Ic）化合物及其亚属和种；含有这些化合物的个人用品；以及这些化合物和个人用品的用途，特别是增加或诱导化学麻醉感觉的用途，如冷却或冷感。
• FIVE-MEMBERED HETEROCYLIC COMPOUNDS USEFUL AS MODULATORS OF TRPM8
  申请人：Firmenich Incorporated

  公开号：EP3461816B1

  公开（公告）日：2021-03-24
• US4921855A
  申请人：——

  公开号：US4921855A

  公开（公告）日：1990-05-01
• US5142048A
  申请人：——

  公开号：US5142048A

  公开（公告）日：1992-08-25