(S)-1-Boc-3-羟甲基哌嗪 | 314741-40-7

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: (S)-1-Boc-3-羟甲基哌嗪
• 中文别名: (S)-3-羟甲基哌嗪-1-甲酸叔丁酯；(S)-1-BOC-3-羟甲基哌嗪；S-1-Boc-3-羟甲基哌嗪
• 英文名称: tert-butyl (S)-3-(hydroxymethyl)piperazine-1-carboxylate
• 英文别名: (S)-tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate；tert-butyl (3S)-3-(hydroxymethyl)piperazine-1-carboxylate；(S)-4-N-boc-2-hydroxymethyl piperazine；tert-butyl (S)-3-(hydroxymethyl)piperazin-1-carboxylate
• CAS: 314741-40-7
• 化学式: C₁₀H₂₀N₂O₃
• 分子量: 216.28
• InChiKey: NSILYQWHARROMG-QMMMGPOBSA-N

物化性质

• 沸点：
  322.9±22.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 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：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8℃

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: (S)-1-Boc-3-hydroxymethyl-piperazine
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H318: Causes serious eye damage
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

---

Section 3. Composition/information on ingredients.
Ingredient name: (S)-1-Boc-3-hydroxymethyl-piperazine
CAS number: 314741-40-7

---

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.

---

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.

---

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.

---

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.
Storage: Store in closed vessels, refrigerated.

---

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.

---

Section 9. Physical and chemical properties
Appearance: Not specified
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C10H20N2O3
Molecular weight: 216.3

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

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

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

(S)-1-BOC-3-羟甲基哌嗪是一种有机合成中间体和医药中间体，适用于实验室研发过程及化工医药合成。

制备方法如下： 在200毫升圆底烧瓶中加入(S)-(4-苄基哌嗪-2-基)甲醇(15K)(10.3克，50毫摩尔)和100毫升甲醇。添加碳载氢氧化钯(3.0克)，并对烧瓶进行五次氢气和真空循环处理。将烧瓶置于室温条件下，并与大气氢气一起搅拌过夜。

完成后，通过硅藻土过滤反应产物至布氏漏斗中。将滤液冷却至-15°C，缓慢加入Boc酸酐(10.9克, 等当量)到甲醇溶液中。添加完毕后，将烧瓶加热至0°C并搅拌2小时。

最后，将烧瓶恢复至室温，并在真空条件下除去溶剂。使用4:2乙酸乙酯-甲醇通过柱色谱法纯化残余物，得到15毫升油状物（11.01克，收率85%）。

反应信息

• 作为反应物：
  描述：

  (S)-1-Boc-3-羟甲基哌嗪 在 草酰氯 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 1-benzyl 4-(tert-butyl) 2-formylpiperazine-1,4-dicarboxylate
  参考文献：
  名称：

  [EN] HETEROARYLDIHYDROPYRIMIDINE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS
  [FR] DÉRIVÉS D'HÉTÉROARYLDIHYDROPYRIMIDINE ET PROCÉDÉS DE TRAITEMENT D'INFECTIONS PAR LE VIRUS DE L'HÉPATITE B

  摘要：

  本文提供了用于治疗HBV感染的化合物，包括药物组成和抑制、抑制或预防受试者HBV感染的方法。

  公开号：

  WO2020125730A1
• 作为产物：
  描述：

  (8aS)-四氢-3-氧代-3H-恶唑并[3,4-a]吡嗪-7(1H)-羧酸叔丁酯 在 lithium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 1.5h， 以21 g的产率得到(S)-1-Boc-3-羟甲基哌嗪
  参考文献：
  名称：

  差异保护的2-（羟甲基）哌嗪的实用合成

  摘要：

  从光学活性的和可商购获得的（2 S）-哌嗪-2-羧酸二盐酸盐开始，提出了三种不同保护的2-（羟甲基）哌嗪的有效且可扩展的合成。这些合成构件可用于制备生物活性化合物，并用作构建组合文库的化学支架。

  DOI：

  10.1021/jo701465h

文献信息

• [EN] MACROCYLIC PYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRIDINE MACROCYCLIQUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2015150557A1

  公开（公告）日：2015-10-08

  The present invention relates to substituted macrocylic pyrimidine derivatives of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention have EF2K inhibitory activity and optionally also Vps34 inhibitory activity. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及式（I）的取代大环嘧啶衍生物，其中变量的含义如权利要求中所定义。根据本发明的化合物具有EF2K抑制活性，还可能具有Vps34抑制活性。本发明还涉及制备这种新化合物的方法，包含所述化合物作为活性成分的药物组合物，以及将所述化合物用作药物的用途。
• [EN] AUTOTAXIN INHIBITORS COMPRISING A HETEROAROMATIC RING-BENZYL-AMIDE-CYCLE CORE<br/>[FR] INHIBITEURS DE L'AUTOTAXINE CONTENANT UN NOYAU À CYCLE BENZYLE-AMIDE CYCLIQUE HÉTÉROAROMATIQUE
  申请人：NOVARTIS AG

  公开号：WO2015008230A1

  公开（公告）日：2015-01-22

  The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.

  本发明涉及新型化合物，这些化合物是自体磷脂酶抑制剂，涉及它们的制备方法，含有它们的药物组合物和药物，以及它们在由自体磷脂酶介导的疾病和紊乱中的应用。
• Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRAS^G12C
  作者：Jason G. Kettle、Sharan K. Bagal、Sue Bickerton、Michael S. Bodnarchuk、Jason Breed、Rodrigo J. Carbajo、Doyle J. Cassar、Atanu Chakraborty、Sabina Cosulich、Iain Cumming、Michael Davies、Andrew Eatherton、Laura Evans、Lyman Feron、Shaun Fillery、Emma S. Gleave、Frederick W. Goldberg、Stephanie Harlfinger、Lyndsey Hanson、Martin Howard、Rachel Howells、Anne Jackson、Paul Kemmitt、Jennifer K. Kingston、Scott Lamont、Hilary J. Lewis、Songlei Li、Libin Liu、Derek Ogg、Christopher Phillips、Radek Polanski、Graeme Robb、David Robinson、Sarah Ross、James M. Smith、Michael Tonge、Rebecca Whiteley、Junsheng Yang、Longfei Zhang、Xiliang Zhao

  DOI：10.1021/acs.jmedchem.9b01720

  日期：2020.5.14

  efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket on GDP-bound RAS, locking it in an inactive state. A weak inhibitor at this site was optimized through conformational locking of a piperazine-quinazoline motif and linker modification

  尽管工业界和学术界做出了许多努力，但直接为重要的癌基因KRAS服药的尝试取得了有限的成功。KRASG12C突变体代表“致命弱点”，最近已与小分子共价靶向，这些小分子与突变体半胱氨酸结合并在GDP结合的RAS上形成一个变构口袋，从而将其锁定在非活性状态。通过哌嗪-喹唑啉基序的构象锁定和接头修饰优化了该位点的弱抑制剂。随后在哌嗪中引入关键甲基会导致效力，通透性，清除率和反应性增强，从而鉴定出具有高选择性，出色的跨物种药代动力学参数和体内功效的有效KRASG12C抑制剂。
• [EN] HETEROARYL COMPOUNDS THAT INHIBIT G12C MUTANT RAS PROTEINS<br/>[FR] COMPOSÉS HÉTÉROARYLE INHIBANT DES PROTÉINES RAS PORTANT LA MUTATION G12C
  申请人：ASTRAZENECA AB

  公开号：WO2018206539A1

  公开（公告）日：2018-11-15

  The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

  该规范涉及到式（I）的化合物及其药用盐。该规范还涉及用于它们制备的过程和中间体，含有它们的药物组合物以及它们在治疗细胞增殖性疾病中的用途。
• [EN] TETRACYCLIC HETEROARYL COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROARYLES TÉTRACYCLIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2019215203A1

  公开（公告）日：2019-11-14

  The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

  该规范涉及到式（I）的化合物及其药用盐。该规范还涉及用于它们制备的过程和中间体，含有它们的药物组合物以及它们在治疗细胞增殖性疾病中的用途。