(3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯 | 714971-28-5

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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: (3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯
• 中文别名: (S)-N-Boc-3-(羟甲基)吗啉；(S)-4-Boc-3-吗啉甲醇；3(S)-羟基甲基-4-boc吗啉；(S)-N-BOC-3-羟甲基吗啉；(S)-4-BOC-3-吗啉甲醇
• 英文名称: (S)-tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate
• 英文别名: tert-butyl (3S)-3-(hydroxymethyl)morpholine-4-carboxylate；tert-butyl (S)-3-(hydroxymethyl)morpholine-4-carboxylate
• CAS: 714971-28-5
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: AIQSXVGBMCJQAG-QMMMGPOBSA-N

物化性质

• 熔点：
  80 ºC
• 沸点：
  320.7±27.0 °C(Predicted)
• 密度：
  1.118

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (S)-3-Hydroxymethyl-4-boc-morpholine
Synonyms: tert-Butyl (3S)-3-(hydroxymethyl)morpholine-4-carboxylate

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: (S)-3-Hydroxymethyl-4-boc-morpholine
CAS number: 714971-28-5

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C10H19NO4
Molecular weight: 217.3

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

(3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯是合成BMS-599626的关键中间体。BMS-599626是一种人表皮生长因子受体1和2激酶的选择性和口服有效抑制剂。

N-取代吗啉作为一种有机化工中间体，兼具叔胺及醚的双重性质，应用广泛。它可作为聚氨酯泡沫生产的催化剂、阿扑西林、氨基苄青霉素及羧基苄青霉素合成过程中的催化剂，还能用作表面活性剂、萃取剂和腐蚀抑制剂。N-甲基氧化吗啉是其衍生物，也是制造Lyocell天然纤维和Newcell人造纤维长丝的理想纺丝溶剂。

制备

(3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯含有叔胺和醚的双重基团，不仅是半合成青霉素和聚氨酯发泡过程中重要的催化剂，还是合成N-取代氧化吗啉的重要原材料。当前主要合成工艺包括吗啉法、N-甲基二乙醇胺法、二乙醇胺法、二甘醇法和二氯乙醚法。

(3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯的制备以(R)-(4-苄基-3-吗啡啉)-甲醇为起始物料，经与二碳酸二叔丁酯反应制备。合成反应式如下图所示：

实验操作步骤如下： 向(R)-(4-苄基-3-吗啡啉)-甲醇的二氯甲烷溶液中加入三乙胺，滴加二碳酸二叔丁酯的二氯甲烷溶液。滴毕后，反应15小时，减压蒸除溶剂，浓缩物经硅胶柱层析（洗脱剂：V（乙酸乙酯）/ V (石油醚) = 1/10）纯化，最终得到化合物(3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯。

反应信息

• 作为反应物：
  描述：

  (3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯 在 盐酸 作用下， 以 甲醇 为溶剂， 以100%的产率得到(S)-3-羟甲基吗啉盐酸盐
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  本发明涉及抑制Lp-PLA2活性的新化合物，其制备方法，含有这些化合物的组合物以及它们在治疗与Lp-PLA2活性相关的疾病中的应用，例如阿尔茨海默病。

  公开号：

  WO2016011930A1
• 作为产物：
  描述：

  (3R)-3,4-吗啉二羧酸 4-叔丁酯 在 diborane(6) 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 (3S)-3-(羟甲基)吗啉-4-羧酸叔丁酯
  参考文献：
  名称：

  具有2-氨基吡啶骨架的有效和选择性人神经元一氧化氮合酶抑制剂对血脑屏障通透性的优化。

  摘要：

  由于血脑屏障（BBB），有效地将治疗药物输送到人脑是中枢神经系统药物开发中最具挑战性的任务之一。为了克服BBB，必须同时解决化合物的被动渗透性和外向转运蛋白的责任。在这里，我们报告了我们的优化与神经元一氧化氮合酶（nNOS）抑制剂的BBB渗透有关，以开发用于神经退行性疾病的新药。已经采用了各种方法，包括增强新抑制剂的亲脂性和刚性以及调节氨基的p Ka。除了确定抑制剂的效力和选择性外，还确定了与各种一氧化氮合酶同工型复合的大多数新设计化合物的晶体结构。我们发现了一个新的类似物（21），

  DOI：

  10.1021/acs.jmedchem.8b02032

文献信息

• [EN] IMMUNOPROTEASOME INHIBITORS<br/>[FR] INHIBITEURS D'IMMUNOPROTÉASOME
  申请人：PRINCIPIA BIOPHARMA INC

  公开号：WO2018136401A1

  公开（公告）日：2018-07-26

  Provided herein are compounds, such as a compound of Formula (I), as described herein, or a pharmaceutically acceptable salt thereof, that are immunoproteasome (such as LMP2 and LMP7) inhibitors. The compounds described herein can be useful for the treatment of diseases treatable by inhibition of immunoproteasomes. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本文提供了化合物，例如所述的化合物的化学式(I)，或其药用可接受的盐，这些化合物是免疫蛋白酶体（如LMP2和LMP7）抑制剂。本文描述的化合物可用于治疗通过抑制免疫蛋白酶体可治疗的疾病。本文还提供了含有这些化合物的药物组合物以及制备这些化合物的方法。
• [EN] ERBB/BTK INHIBITORS<br/>[FR] INHIBITEURS DE ERBB/BTK
  申请人：DIZAL JIANGSU PHARMACEUTICAL CO LTD

  公开号：WO2019149164A1

  公开（公告）日：2019-08-08

  Disclosed are compounds inhibiting ErbBs (e. g., EGFR or Her 2), especially mutant forms of ErbBs, and BTK, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compound and the pharmaceutical composition can effectively treat ErbBs (especially mutant forms of ErbBs) or BTK associated diseases, including cancer.

  揭示了抑制ErbBs（例如EGFR或Her 2），特别是ErbBs的突变形式，以及BTK的化合物，其药用盐、水合物、溶剂合物或立体异构体，以及包含这些化合物的药物组合物。该化合物和药物组合物可以有效治疗ErbBs（特别是ErbBs的突变形式）或与BTK相关的疾病，包括癌症。
• Di-substituted pyrrolotrizine compounds
  申请人：Gavai V. Ashvinikumar

  公开号：US20050197339A1

  公开（公告）日：2005-09-08

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The compounds of the invention inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.

  本发明提供了式I的化合物及其药用盐。本发明的化合物抑制生长因子受体的酪氨酸激酶活性，如HER1、HER2和HER4，从而使它们在癌症和其他疾病治疗中作为抗增殖剂具有用途。
• [EN] DIHYDROPYRIMIDINE COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS<br/>[FR] COMPOSÉS DIHYDROPYRIMIDINE ET LEUR APPLICATION DANS DES PRODUITS PHARMACEUTIQUES
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2015144093A1

  公开（公告）日：2015-10-01

  Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein the variables of the formulas are as defined in the specification. Also provided herein is the use of the compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof for treating and preventing HBV diseases.

  本文提供了二氢嘧啶化合物及其药物应用，特别是用于治疗和预防HBV疾病。具体而言，本文提供了具有化学式（I）或（Ia）的化合物，或其对映体、二对映体、互变异构体、水合物、溶剂合物或其药用可接受的盐，其中化学式的变量如规范中所定义。本文还提供了使用具有化学式（I）或（Ia）的化合物，或其对映体、二对映体、互变异构体、水合物、溶剂合物或其药用可接受的盐来治疗和预防HBV疾病。
• [EN] PIPERAZINES AS ANTI-OBESITY AGENTS<br/>[FR] PIPÉRAZINES COMME AGENTS ANTI-OBÉSITÉ
  申请人：BIOVITRUM AB PUBL

  公开号：WO2009071658A1

  公开（公告）日：2009-06-11

  The present invention relates to new compounds of formula (I), to pharmaceutical compositions comprising these compounds, to processes for their preparation, and to the use of these compounds as leptin receptor modulator mimetics in the preparation of medicaments against conditions associated with weight gain, type 2 diabetes and dyslipidemias.

  本发明涉及公式（I）的新化合物，包括这些化合物的药物组合物，其制备方法，以及将这些化合物用作在制备针对与体重增加、2型糖尿病和血脂异常相关疾病的药物中的瘦素受体调节剂拟拟物。