(S)-1-N-Boc-2-甲基哌嗪 | 169447-70-5

• 物质功能分类: 医药中间体 - 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-N-Boc-2-甲基哌嗪
• 中文别名: (S)-2-甲基哌嗪-1-甲酸叔丁酯；(S)-1-叔丁氧羰-2-甲基-哌嗪；S-1-Boc-2-甲基哌嗪；S-N-BOC-2-甲基哌嗪；(S)-1-BOC-2-甲基哌嗪；(S)-1-Boc-2-甲基哌嗪
• 英文名称: (S)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: (S)-tert-butyl 2-methylpiperazine-1-carboxylate；tert-butyl (S)-2-methylpiperazine-1-carboxylate；tert-butyl (2S)-2-methylpiperazine-1-carboxylate；(S)-1-N-Boc-2-methylpiperazine；(S)-1-boc-2-methylpiperazine；(S)-1-N-tert-butoxy carbonyl-2-methylpiperazine；(S)-1-(tert-butoxycarbonyl)-2-methylpiperazine；tert-butyl (S)-2-methylpiperazin-1-carboxylate
• CAS: 169447-70-5
• 化学式: C₁₀H₂₀N₂O₂
• mdl: MFCD01862121
• 分子量: 200.281
• InChiKey: DATRVIMZZZVHMP-QMMMGPOBSA-N

物化性质

• 熔点：
  43.0 to 47.0 °C
• 沸点：
  268.7±15.0 °C(Predicted)
• 密度：
  0.997±0.06 g/cm3(Predicted)
• 溶解度：
  溶于甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

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：
  存放于惰性气体中，并避免接触湿气（尤其是潮湿环境）。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (S)-1-N-Boc-2-methylpiperazine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H411: Toxic to aquatic life with long lasting effects
P273: Avoid release to the environment

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Section 3. Composition/information on ingredients.
Ingredient name: (S)-1-N-Boc-2-methylpiperazine
CAS number: 169447-70-5

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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.
Storage: Store in closed vessels, refrigerated.

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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
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C10H20N2O2
Molecular weight: 200.3

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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

在药物化学、有机化学及材料领域，(S)-1-N-Boc-2-甲基哌嗪具有广泛的应用，并且是抗精神病药物工艺研究中的关键中间体。

合成方法

通过以下步骤合成了(S)-1-N-Boc-2-甲基哌嗪：

1. 步骤a：首先，在室温条件下，将2克(20 mmol) (S)-2-甲基哌嗪溶解在200毫升THF中，并加入40毫米摩尔、25毫升1.6 M己烷溶液的n-BuLi。搅拌30分钟后，滴加3.04克(20 mmol) TBDMSCl。混合物继续搅拌一个小时后，再添加5.2克(24 mmol) (Boc)2O。反应混合物在室温下搅拌一小时后，用50毫升水稀释。分离有机层，并用50毫升盐水洗涤，在Na2SO4上干燥并浓缩。

   快速硅胶色谱（使用5% MeOH/2% NH4OH/93% CH2Cl2）提供了黄色油状目标化合物(S)-1-N-Boc-2-甲基哌嗪(3.7克，产率93%)。

合成路线

图展示了(S)-1-N-Boc-2-甲基哌嗪的合成路线。

反应信息

• 作为反应物：
  描述：

  (S)-1-N-Boc-2-甲基哌嗪 在 三乙酰氧基硼氢化钠 、 铁粉 、 氯化铵 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 tert-butyl (2S)-4-[(4-aminophenyl)methyl]-2-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  WO2007/144400

  摘要：

  公开号：
• 作为产物：
  描述：

  2,5-哌嗪二酮,3-甲基-1-(苯基甲基)-,(3S)- 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 80.0h， 生成 (S)-1-N-Boc-2-甲基哌嗪
  参考文献：
  名称：

  A Novel and Facile Method to Synthesize (R)‐ and (S)‐2‐methylpiperazine

  摘要：

  A concise and efficient synthesis of (R)- and (S)-2-methylpiperazine in only five steps from (D)- and (L)-alanine is described. The key step is reaction of benzylamine with a bifunctional molecule to build a six-membered ring.

  DOI：

  10.1081/scc-200036590
• 作为试剂：
  描述：

  4-溴乙基苯乙酸甲酯 、 (S)-1-N-Boc-2-甲基哌嗪 在 (S)-1-N-Boc-2-甲基哌嗪 作用下， 以95的产率得到(S)-4-(4-(2-甲氧基-2-氧代乙基)苄基)-2-甲基哌嗪-1-甲酸叔丁酯
  参考文献：
  名称：

  J. Med. Chem. 2009, 52, 1180-1189

  摘要：

  DOI：

文献信息

• Dual Pharmacophores - PDE4-Muscarinic Antagonistics
  申请人：Callahan James Francis

  公开号：US20090203657A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2015180612A1

  公开（公告）日：2015-12-03

  Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.

  揭示了新型视黄醇相关孤儿受体γ（RORγ）调节剂及其在通过RORγ介导的疾病治疗中的应用。
• Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development
  作者：James J. Crawford、Adam R. Johnson、Dinah L. Misner、Lisa D. Belmont、Georgette Castanedo、Regina Choy、Melis Coraggio、Liming Dong、Charles Eigenbrot、Rebecca Erickson、Nico Ghilardi、Jonathan Hau、Arna Katewa、Pawan Bir Kohli、Wendy Lee、Joseph W. Lubach、Brent S. McKenzie、Daniel F. Ortwine、Leah Schutt、Suzanne Tay、BinQing Wei、Karin Reif、Lichuan Liu、Harvey Wong、Wendy B. Young

  DOI：10.1021/acs.jmedchem.7b01712

  日期：2018.3.22

  Bruton’s tyrosine kinase (Btk) is a nonreceptor cytoplasmic tyrosine kinase involved in B-cell and myeloid cell activation, downstream of B-cell and Fcγ receptors, respectively. Preclinical studies have indicated that inhibition of Btk activity might offer a potential therapy in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the discovery and preclinical

  布鲁顿酪氨酸激酶（Btk）是一种非受体胞质酪氨酸激酶，分别参与B细胞和髓样细胞活化，位于B细胞和Fcγ受体的下游。临床前研究表明，抑制Btk活性可能为类风湿性关节炎和系统性红斑狼疮等自身免疫性疾病提供潜在的治疗方法。在这里，我们公开了目前在临床开发中的有效，选择性和非共价Btk抑制剂的发现和临床前表征。GDC-0853（29）抑制B细胞和髓细胞介导的疾病成分，并在体内表现出剂量依赖性活性炎性关节炎大鼠模型。它在类风湿性关节炎，狼疮和慢性自发性荨麻疹患者的临床前和2期研究中显示出非常有利的安全性，药代动力学（PK）和药效学（PD）概况。根据其效价，选择性，长目标停留时间和非共价抑制模式，29在广泛的免疫学适应症中具有成为同类最佳Btk抑制剂的潜力。
• [EN] 2,3-DISUBSTITUTED 1 -ACYL-4-AMINO-1,2,3,4-TETRAHYDROQUINOLINE DERIVATIVES AND THEIR USE AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS 2,3-DISUBSTITUÉS DE 1-ACYL-4-AMINO-1,2,3,4-TÉTRAHYDROQUINOLÉINE ET LEUR UTILISATION COMME INHIBITEURS DE BROMODOMAINES
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2014140076A1

  公开（公告）日：2014-09-18

  The present invention relates to novel compounds of formula (I), wherein R1 is C1-4alkyl; R2 is C1-4alkyl, C3-7cycloalkyl, -CH2CF3, -CH2OCH3 or heterocyclyl; R3 is C1-4alkyl, -CH2F, -CH2OH or -CH2O(O)CH3; R4 when present is as defined in claim 1; R5 when present is H, halo, hydroxy or C1-6alkoxy; A is -NH-, -O-, -S-, -SO-, -SO2-, -N(C1-4alkyl)- or -NC(O)(CH3)-; V is phenyl, heteroaromatic or pyridone any of which may be optionally substituted by 1, 2 or 3 substituents; W is CH or N; X is C or N; Y is C or N; and Z is CH or N; subject to the proviso that no more than 2 of W, X, Y and Z are N, pharmaceutical compositions containing such compounds and to their use as bromodomain inhibitors.

  本发明涉及式(I)的新化合物，其中R1为C1-4烷基；R2为C1-4烷基、C3-7环烷基、-CH2CF3、-CH2OCH3或杂环烷基；R3为C1-4烷基、-CH2F、-CH2OH或-CH2O(O)CH3；R4存在时如权利要求1所定义；R5存在时为H、卤素、羟基或C1-6烷氧基；A为-NH-、-O-、-S-、-SO-、-SO2-、-N(C1-4烷基)-或-NC(O)(CH3)-；V为苯基、杂芳基或吡啶酮，其中任何一个可以选择性地被1、2或3个取代基取代；W为CH或N；X为C或N；Y为C或N；Z为CH或N；但W、X、Y和Z中不超过2个为N，含有这种化合物的药物组合物以及它们作为溴结构域抑制剂的用途。
• PYRROLE mTORC INHIBITORS AND USES THEREOF
  申请人：Navitor Pharmaceuticals, Inc.

  公开号：US20190389843A1

  公开（公告）日：2019-12-26

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用这些化合物的方法。