(3R)-3-(羟甲基)吗啉-4-羧酸叔丁酯 | 215917-99-0

• 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: (3R)-3-(羟甲基)吗啉-4-羧酸叔丁酯
• 中文别名: (R)-N-BOC-3-羟甲基吗啉；3(R)-羟基甲基-4-boc吗啉；(R)-N-Boc-3-吗啉甲醇；(R)-4-Boc-3-吗啉甲醇；(R)-4-BOC-3-吗啉甲醇
• 英文名称: (R)-tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate
• 英文别名: tert-butyl (3R)-3-(hydroxymethyl)morpholine-4-carboxylate；tert-butyl (R)-3-(hydroxymethyl)morpholine-4-carboxylate
• CAS: 215917-99-0
• 化学式: C₁₀H₁₉NO₄
• mdl: MFCD06799477
• 分子量: 217.265
• InChiKey: AIQSXVGBMCJQAG-MRVPVSSYSA-N

物化性质

• 沸点：
  320.7±27.0 °C(Predicted)
• 密度：
  1.118±0.06 g/cm3(Predicted)

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,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (R)-3-Hydroxymethyl-4-boc-morpholine
Synonyms: tert-Butyl (3R)-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: (R)-3-Hydroxymethyl-4-boc-morpholine
CAS number: 215917-99-0

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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

(3R)-3-(羟甲基)吗啉-4-羧酸叔丁酯是合成BMS-599626的关键中间体，而BMS-599626是一种选择性地抑制人表皮生长因子受体1和2激酶且具有口服效果的抑制剂。

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。它不仅可作为聚氨酯泡沫生产的催化剂，还在阿扑西林、氨基苄青霉素及羧基苄青霉素合成过程中发挥作用。此外，N-取代吗啉还可用作表面活性剂、萃取剂和腐蚀抑制剂；其衍生物N-甲基氧化吗啉是制造Lyocell天然纤维和Newcell人造纤维长丝的理想纺丝溶剂。

制备

N-取代吗啉含有叔胺和醚的双重基团，不仅在半合成青霉素和聚氨酯发泡过程中作为重要的催化剂使用，还用于合成N-取代氧化吗啉。当前合成工艺主要包括吗啉法、N-甲基二乙醇胺法、二乙醇胺法、二甘醇法和二氯乙醚法。

(3R)-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，通过与二碳酸二叔丁酯反应制备。合成反应式如下图：

合成反应式

-3-(羟甲基)吗啉-4-羧酸叔丁酯合成反应式)

实验操作步骤

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。滴加完毕后，进行15小时反应，然后减压蒸除溶剂，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(3R)-3-(羟甲基)吗啉-4-羧酸叔丁酯。

反应信息

• 作为反应物：
  描述：

  (3R)-3-(羟甲基)吗啉-4-羧酸叔丁酯 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以495 mg的产率得到(S)-3-醛基-4-Boc-吗啉
  参考文献：
  名称：

  [EN] DIHYDROPYRIMIDINYLTHIAZOLE FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
  [FR] DIHYDROPYRIMIDINYLTHIAZOLE POUR LE TRAITEMENT ET LA PROPHYLAXIE D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B

  摘要：

  本发明提供具有以下一般式的新化合物：其中R1、R2、X、Y和A如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。

  公开号：

  WO2019129681A1
• 作为产物：
  描述：

  (3S)-3,4-吗啉二羧酸 4-叔丁酯 在 硼烷四氢呋喃络合物 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以45.2%的产率得到(3R)-3-(羟甲基)吗啉-4-羧酸叔丁酯
  参考文献：
  名称：

  [EN] 3-(5-METHOXY-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS DE 3-(5-MÉTHOXY-1-OXOISOINDOLIN-2-YL)PIPÉRIDINE-2,6-DIONE ET LEURS UTILISATIONS

  摘要：

  本公开涉及式(I')的化合物、药物组合物及其在降低广泛间隔锌指蛋白结构域（WIZ）表达水平、诱导胎儿血红蛋白（HbF）表达以及治疗遗传性血液疾病（例如，血红蛋白病，例如，β-血红蛋白病）方面的用途，如镰状细胞病和β-地中海贫血。

  公开号：

  WO2021124172A1

文献信息

• [EN] NOVEL PYRAZOLO-PYRROLO-PYRIMIDINE-DIONE DERIVATIVES AS P2X3 INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE PYRAZOLO-PYRROLO-PYRIMIDINE-DIONE UTILISÉS EN TANT QU'INHIBITEURS DE P2X3
  申请人：BAYER AG

  公开号：WO2019081343A1

  公开（公告）日：2019-05-02

  The present invention covers substituted Pyrazolo-pyrrolo-pyrimidine-dione (PPPD) compounds of general formula (I): in which R1, R2 and R3 are as defined herein, methods of preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of neurogenic diseases, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式(I)的取代吡唑基-吡咯基-嘧啶二酮（PPPD）化合物：其中R1、R2和R3如本文所定义，制备所述化合物的方法，包含所述化合物的药物组合物和配方，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是神经源性疾病，作为唯一活性成分或与其他活性成分组合使用。
• [EN] N-(ARYLALKYL)-N'-PYRAZOLYL-UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS<br/>[FR] COMPOSÉS DE N-(ARYLALKYLE)-N'-PYRAZOLYLE-URÉE, DE THIOURÉE, DE GUANIDINE ET DE CYANOGUANIDINE EN TANT QU'INHIBITEURS DE LA KINASE TRKA
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2014078331A1

  公开（公告）日：2014-05-22

  Compounds of Formula I or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C, X, Ra, Rb, Rc, Rd and n are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.

  公式I的化合物或立体异构体、互变异构体、或药用可接受的盐、溶剂化物或前药，其中环A、环C、X、Ra、Rb、Rc、Rd和n如本文所述定义，是TrkA激酶的抑制剂，可用于治疗可以用TrkA激酶抑制剂治疗的疾病，如疼痛、癌症、炎症/炎症性疾病、神经退行性疾病、某些传染病、舍格伦综合症、子宫内膜异位症、糖尿病周围神经病变、前列腺炎或骨盆疼痛综合征。
• NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION AND USE
  申请人：Shanghai Pharmaceuticals Holding Co., Ltd.

  公开号：EP3424928A1

  公开（公告）日：2019-01-09

  Disclosed are a nitrogenous heterocyclic compound, intermediates, a preparation method, a composition and use thereof. The nitrogenous heterocyclic compound in the present invention is as shown in formula I. The compound has a high inhibitory activity towards ErbB2 tyrosine kinase and a relatively good inhibitory activity towards human breast cancer BT-474 and human gastric cancer cell NCI-N87 which express ErbB2 at a high level, and at the same time has a relatively weak inhibitory activity towards EGFR kinase. Namely, the compound is a highly selective small-molecule inhibitor targeted at ErbB2, and hence it has a high degree of safety, and can effectively enlarge the safety window in the process of taking the drug.

  本公开揭示了一种含氮杂环化合物、中间体、制备方法、组合物及其用途。本发明中的含氮杂环化合物如公式I所示。该化合物对ErbB2酪氨酸激酶具有较高的抑制活性，并且对人类乳腺癌BT-474和人类胃癌细胞NCI-N87表达ErbB2的抑制活性相对较好，同时对EGFR激酶具有相对较弱的抑制活性。换句话说，该化合物是一种高度选择性的针对ErbB2的小分子抑制剂，因此具有很高的安全度，并且可以有效地扩大服药过程中的安全窗口。
• [EN] SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS<br/>[FR] COMPOSÉS PYRAZOLO[1,5-A]PYRIMIDINE SUBSTITUÉS UTILISÉS COMME INHIBITEURS DE MTOR
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2011029027A1

  公开（公告）日：2011-03-10

  Compounds of Formula I: and salts thereof in which R1, R2, R2a, R3, n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.

  公式I的化合物：以及其中R1、R2、R2a、R3、n、X和环B具有说明书中给出的含义的盐，是mTOR的抑制剂，可用于治疗对mTOR抑制敏感的疾病，如癌症。
• [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。