(2R,4S)-N-BOC-4-羟基哌啶-2-甲酸甲酯 | 321744-26-7

• 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 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (2R,4S)-N-BOC-4-羟基哌啶-2-甲酸甲酯
• 中文别名: (2R,4S)-N-BOC-4-羟基哌啶-2-羧酸甲酯
• 英文名称: N-Boc-4-hydroxy-2-piperidine carboxylic acid methyl ester
• 英文别名: (2R,4S)-1-tert-butyl 2-methyl 4-hydroxypiperidine-1,2-dicarboxylate；(2R,4S)-N-(tert-butoxycarbonyl)-4-hydroxypiperidine-2-carboxylic acid methyl ester；(2R,4S)-4-hydroxy-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester；(2R,4S)-N-boc-4-hydroxypiperidine-2-carboxylic acid methyl ester；1-O-tert-butyl 2-O-methyl (2R,4S)-4-hydroxypiperidine-1,2-dicarboxylate
• CAS: 321744-26-7
• 化学式: C₁₂H₂₁NO₅
• mdl: MFCD02259744
• 分子量: 259.302
• InChiKey: RNMVWSAJMIKMDY-DTWKUNHWSA-N

物化性质

• 沸点：
  402.56°C (rough estimate)
• 密度：
  1.182
• 稳定性/保质期：
  遵循规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 安全说明：
  S24/25
• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存放于4℃阴凉干燥处

SDS

Name:	(2R 4S)-N-BOC-4-Hydroxypiperidine-2-Carboxylic Acid Methyl Ester Material Safety Data Sheet
Synonym:	Methyl (2R,4S)-N-BOC-4-Hydroxypiperidine-2-Carboxylate
CAS:	321744-26-7

Section 1 - Chemical Product MSDS Name:(2R 4S)-N-BOC-4-Hydroxypiperidine-2-Carboxylic Acid Methyl Ester Material Safety Data Sheet
Synonym:Methyl (2R,4S)-N-BOC-4-Hydroxypiperidine-2-Carboxylate

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
321744-26-7	(2R,4S)-N-BOC-4-Hydroxypiperidine-2-Ca	95%	unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 321744-26-7: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white to off-white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C12H21NO5
Molecular Weight: 259.30

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Incompatible materials, dust generation.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 321744-26-7 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(2R,4S)-N-BOC-4-Hydroxypiperidine-2-Carboxylic Acid Methyl Ester - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 321744-26-7: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 321744-26-7 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 321744-26-7 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (2R,4S)-N-BOC-4-羟基哌啶-2-甲酸甲酯 在 吡啶 、 4-二甲氨基吡啶 、 sodium azide 、 palladium 10% on activated carbon 、 水 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 65.0 ℃ 、344.75 kPa 条件下， 反应 79.0h， 生成 格拉斯吉布
  参考文献：
  名称：

  PF-04449913 的发现，一种有效的口服生物可利用的平滑抑制剂

  摘要：

  Hedgehog 信号通路的抑制剂在肿瘤学领域引起了极大的兴趣，因为越来越多的证据表明它们有潜力为患者提供有希望的治疗选择。在此，我们描述了克服先导结构1中固有问题的发现策略，这些问题导致了 Smoothened 抑制剂 1-((2 R ,4 R )-2-(1 H- benzo[ d ]imidazol-2-yl )-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (PF-04449913, 26 )，已进入人体临床研究。

  DOI：

  10.1021/ml2002423
• 作为产物：
  描述：

  methyl (2R,4S)-4-hydroxy-1-((R)-1-phenylethyl)piperidine-2-carboxylate 在 palladium on activated charcoal 、 甲酸铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 19.0h， 生成 (2R,4S)-N-BOC-4-羟基哌啶-2-甲酸甲酯
  参考文献：
  名称：

  The discovery of CCR3/H1 dual antagonists with reduced hERG risk

  摘要：

  A series of dual CCR3/H-1 antagonists based on a bispiperidine scaffold were discovered. Introduction of an acidic group overcame hERG liability. Bioavailability was optimised by modulation of physico-chemical properties and physical form to deliver a compound suitable for clinical evaluation. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.124

文献信息

• BENZIMIDAZOLE DERIVATIVES
  申请人：Munchhof Michael J.

  公开号：US20090005416A1

  公开（公告）日：2009-01-01

  The present invention relates to a compound of the Formula I or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3A , R 3B , R 4 , R 5 , X, m, and n are as defined herein. Such novel benzamidazole derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及一种具有化学式I的化合物或其药用可接受盐，其中R1、R2、R3A、R3B、R4、R5、X、m和n如本文所定义。这种新型苯并咪唑衍生物在治疗哺乳动物（如癌症）的异常细胞生长方面非常有用。本发明还涉及一种使用这种化合物在哺乳动物（尤其是人类）中治疗异常细胞生长的方法，以及含有这种化合物的药物组合物。
• New substituted isoquinoline and isoquinolinone derivatives
  申请人：PLETTENBURG Oliver

  公开号：US20100056566A1

  公开（公告）日：2010-03-04

  The invention relates to 6-substituted isoquinoline and isochinolone derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.

  这项发明涉及用于治疗和/或预防与Rho激酶和/或Rho激酶介导的肌球蛋白轻链磷酸酶磷酸化相关疾病的公式(I)的6-取代异喹啉和异喹啉衍生物，以及含有这类化合物的组合物。
• Synthesis of Free andNα-Fmoc-/Nγ-Boc-Protected (2S,4S)- and (2S,4R)-4-Aminopipecolic Acids
  作者：Fabrizio Machetti、Franca M. Cordero、Francesco De Sarlo、Anna M. Papini、Maria C. Alcaro、Alberto Brandi

  DOI：10.1002/ejoc.200400045

  日期：2004.7

  bearing orthogonal Nα/Nγ-protection suitable for solid-phase peptide synthesis, is reported. These amino acids were synthesised from enantiopure ethyl (2S)-4-oxo-1-(1-phenylethyl)piperidine-2-carboxylate (1) with introduction of the side-chain amino group by reductive amination, followed by protection/deprotection of the functional groups. A mixture of Fmoc-Sly(Boc)-OH 6 and 7 was used to establish their

  报道了 (2S,4S)- 和 (2S,4R)-4-氨基哌啶酸的制备，这是一种构象受限的碱性氨基酸，具有适用于固相肽合成的正交 Nα/Nγ 保护。这些氨基酸由对映体纯乙基 (2S)-4-oxo-1-(1-phenylethyl)piperidine-2-carboxylate (1) 合成，通过还原胺化引入侧链氨基，然后保护/脱保护官能团。Fmoc-Sly(Boc)-OH 6 和 7 的混合物用于建立它们在固相肽合成中的相容性。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
• Synthesis of all isomers of pulcherrimine, a bitter principle in the sea urchin ovary
  作者：Noriko U Sata、Ryuji Kuwahara、Yuko Murata

  DOI：10.1016/s0040-4039(01)02095-0

  日期：2002.1

  All eight isomers of pulcherrimine, a bitter principle of the sea urchin (Hemicentrotus pulcherrimus) ovary have been synthesized, which led to revision of the absolute stereochemistry of pulcherrimine. The synthetic pulcherrimine and the 2S isomer were highly bitter at a concentration of 1.0 mM.

  全部八个异构体pulcherrimine的，海胆（的原则苦马粪）卵巢已经被合成，从而导致pulcherrimine的绝对构型的修订。合成的Pulcherrimine和2 S异构体在1.0 mM的浓度下具有很高的苦味。
• Benzimidazole derivatives
  申请人：Pfizer Inc.

  公开号：US08148401B2

  公开（公告）日：2012-04-03

  The present invention relates to a compound of the Formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3A, R3B, R4, R5, X, m, and n are as defined herein. Such novel benzamidazole derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R1、R2、R3A、R3B、R4、R5、X、m和n如本文所定义。这些新型苯甲酰咪唑衍生物在哺乳动物中治疗异常细胞生长，如癌症等方面有用。本发明还涉及使用这些化合物治疗哺乳动物，特别是人类中的异常细胞生长的方法，以及包含这些化合物的药物组合物。