4-叔丁氧羰基-2(S)-哌嗪叔丁酰胺 | 150323-35-6

• 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: 4-叔丁氧羰基-2(S)-哌嗪叔丁酰胺
• 中文别名: (S)-2-叔丁酰氨基-4-叔丁氧基羰基哌嗪
• 英文名称: N-tert-butyl-4-N-dimethylethylcarbamoyl-2S-piperazine carboxamide
• 英文别名: (S)-3-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperazinecarboxylic acid 1,1-dimethylethyl ester；(S)-2-tert-butylcarboxamide-4-tert-butoxycarbonylpiperazine；t-butyl (S)-3-(tert-butylcarbamoyl)-piperazine-1-carboxylate；(S)-(+)-N-t-butyl-4-t-butoxycarbonyl-2-piperazinecarboxamide；(s)-Tert-butyl 3-(tert-butylcarbamoyl)piperazine-1-carboxylate；tert-butyl (3S)-3-(tert-butylcarbamoyl)piperazine-1-carboxylate
• CAS: 150323-35-6
• 化学式: C₁₄H₂₇N₃O₃
• mdl: MFCD02682987
• 分子量: 285.387
• InChiKey: NASIOHFAYPRIAC-JTQLQIEISA-N

物化性质

• 熔点：
  105-109 °C

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.857
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 海关编码：
  2933599090
• 安全说明：
  S26,S37/39
• 危险性防范说明：
  P264,P280,P302+P352,P305+P351+P338,P332+P313,P337+P313,P362
• 危险性描述：
  H315,H319
• 储存条件：
  2-8℃

SDS

Name:	(S)-2-tert-Butylcarboxamide-4-tert-butoxy-carbonyl piperazine Material Safety Data Sheet
Synonym:	None
CAS:	150323-35-6

Section 1 - Chemical Product MSDS Name:(S)-2-tert-Butylcarboxamide-4-tert-butoxy-carbonyl piperazine Material Safety Data Sheet
Synonym:None

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
150323-35-6	(S)-2-t-Butylcarboxamide-4-t-Butoxy-Ca	100	unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation. May cause chemical conjunctivitis.
Skin:
Causes skin irritation.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea.
Inhalation:
Causes respiratory tract irritation. Can produce delayed pulmonary edema.
Chronic:
Effects may be delayed.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately 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. Do NOT use mouth-to-mouth resuscitation.
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:
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. Use with adequate ventilation. Wash clothing before reuse.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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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# 150323-35-6: 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: Not available.
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: C14H27N3O3
Molecular Weight: 285.39

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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, excess heat.
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# 150323-35-6 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(S)-2-t-Butylcarboxamide-4-t-Butoxy-Carbonyl Piperazine - 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
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
IMO
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 150323-35-6: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 150323-35-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 150323-35-6 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

制备方法与用途

化学性质：

• 白色结晶体，熔点为104-108℃。

用途：

• 用作药物茚地那韦的中间体。

反应信息

• 作为反应物：
  描述：

  4-叔丁氧羰基-2(S)-哌嗪叔丁酰胺 在 盐酸 、 异丙醇 作用下， 生成 茚地那韦
  参考文献：
  名称：

  手性非外消旋酰胺烯酸酯与（S）-缩水甘油基甲苯磺酸酯的高度非对映选择性反应。口服活性HIV-1蛋白酶抑制剂L-735,524的合成

  摘要：

  手性酰胺烯酸酯Li-1与（S）-缩水甘油基甲苯磺酸酯11的反应以高非对映体选择性得到环氧化物3，产率为72％。环氧化物3以71％的分离产率转化为口服活性的HIV-1蛋白酶抑制剂L-735,524。

  DOI：

  10.1016/s0040-4039(00)75787-x
• 作为产物：
  描述：

  2-(叔丁氧羰基氧亚氨基)-2-苯乙腈 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.5h， 生成 4-叔丁氧羰基-2(S)-哌嗪叔丁酰胺
  参考文献：
  名称：

  L-735,524：一种有效且可口服生物利用的HIV蛋白酶抑制剂的设计。

  摘要：

  已经开发了一系列具有羟胺戊酰胺过渡态等排体的HIV蛋白酶抑制剂。将碱性胺掺入L-685,434（2）系列的骨架中可提供抗病毒效力，并在动物模型中具有高度改善的药代动力学特征。在分子模型和抑制的酶复合物的X射线晶体结构的指导下，我们能够设计L-735,524。该化合物有效且竞争性抑制HIV-1 PR和HIV-2 PR，Ki值分别为0.52和3.3 nM。它还以25-50 nM的浓度阻止了HIV-1IIIb感染的MT4淋巴样细胞的扩散。迄今为止，已经报道了许多HIV-PR抑制剂，但由于缺乏可接受的口服生物利用度，因此在人体中的研究很少。L-735,524在三种动物模型中具有口服生物利用度，

  DOI：

  10.1021/jm00047a001
• 作为试剂：
  描述：

  4-叔丁氧羰基-2(S)-哌嗪叔丁酰胺 、 1H-indazole-3-carbonyl chloride 在 4-叔丁氧羰基-2(S)-哌嗪叔丁酰胺 作用下， 生成 [1(1S,2R),5(S)]-2,3,5-三脱氧-N-(2,3-二氢-2-羟基-1H-茚-1-基)-5-[2-[(叔丁基氨基)甲酰]-1-哌嗪基]-2-(苯基甲基)-D-赤式-戊酰胺
  参考文献：
  名称：

  WO9502584A2

  摘要：

  公开号：

文献信息

• Asymmetric Synthesis of Chiral Organofluorine Compounds:  Use of Nonracemic Fluoroiodoacetic Acid as a Practical Electrophile and Its Application to the Synthesis of Monofluoro Hydroxyethylene Dipeptide Isosteres within a Novel Series of HIV Protease Inhibitors
  作者：Andrew G. Myers、Joseph K. Barbay、Boyu Zhong

  DOI：10.1021/ja010113y

  日期：2001.8.1

  (diastereomeric ratios 12:1-84:1), efficient and stereoselective routes to each of the four targeted inhibitors were achieved. The optimized synthetic route to the most potent inhibitor (syn,syn-4, K(i) = 2.0 nM) proceeded in seven steps (87% average yield per step) from aminoindanol hydrocinnamide 40 and (S)-fluoroiodoacetic acid, and allowed for the preparation of more than 1 g of this compound. The inhibition

  描述了一系列 HIV 蛋白酶非对映异构体抑制剂（默克 HIV 蛋白酶抑制剂茚地那韦的单氟化类似物）的两种立体选择性途径。这两条路线的特点是通过不对称烷基化反应立体选择性地构建氟化核心亚基。第一代合成基于来自伪麻黄碱 α-氟乙酰胺的烯醇锂与硝基烯烃 12 的共轭加成，这是一种适度的非对映选择性转化。开发了一种更实用的第二代合成路线，该路线基于一种不对称合成有机氟化合物的新方法，通过使用光学活性氟碘乙酸作为亲电子试剂与手性酰胺烯醇化物相结合进行烯醇化物烷基化。用麻黄碱拆分氟碘乙酸可提供 > 或 = 96% ee 的亲电子试剂的对映体形式。与这种稳定且可储存的手性氟化前体的烷基化反应显示出以高度立体定向的方式进行。随着底物控制的 α-氟酮 44 和 45（非对映体比率 12:1-84:1）的顺式或反选择性还原的发展，实现了四种靶向抑制剂中每一种的有效和立体选择性途径。最有效抑制剂 (syn,syn-4
• Process for preparing optically active piperazine derivatives and
  申请人：Yamakawa Chemical Industry Co., Ltd

  公开号：US05792869A1

  公开（公告）日：1998-08-11

  Process for preparing optically active 2-piperazine-carboxylic acid derivatives, particularly S-enantiomer thereof, in high yield and high optical purity on industrial scale. As the optical resolving agents, easily accessible sulfonamides derived from selected optically active amino acids, such as N-tosyl-L-phenylalanine, N-tosyl-D-phenylglycine, N-tosyl-L-alanine or N-tosyl-L-valine, give excellent results. These resolving agents are stable and easily recovered from the reaction mixture and reused. Resolved 2-piperazinecarboxylic acid derivatives are preferably isolated as 4-t-butoxycarbonyl (Boc) derivatives. Diastereomeric salts (an example being shown below) formed as the intermediates of resolution are novel. ##STR1## \x9bIn the formula "Ar" stands for a phenyl or naphthyl group which may be substituted with one to three C1-C6 alkyl groups, halogen atoms, nitro or alkoxy groups; and n=0 or 1.!

  制备光学活性2-哌嗪羧酸衍生物的过程，特别是S-对映体，在工业规模下高产率和高光学纯度。作为光学分离剂，易于获取的磺酰胺衍生物从选择的光学活性氨基酸中得到，例如N-对甲苯磺酰-L-苯丙氨酸，N-对甲苯磺酰-D-苯甘氨酸，N-对甲苯磺酰-L-丙氨酸或N-对甲苯磺酰-L-缬氨酸，效果很好。这些分离剂稳定且易于从反应混合物中回收和再利用。解析的2-哌嗪羧酸衍生物最好作为4-t-叔丁氧羰基（Boc）衍生物分离。分辨率的中间体形成的对映异构体盐（如下面的示例所示）是新颖的。 ##STR1## \x9b在公式中，“Ar”代表苯基或萘基，可以用1至3个C1-C6烷基，卤素原子，硝基或烷氧基替代；n = 0或1！
• Reductive amination process
  申请人：Merck & Co., Inc.

  公开号：US05508404A1

  公开（公告）日：1996-04-16

  A process of reductive amination efficiently yields an HIV protease inhibitor.

  一种还原胺化的过程高效地产生了一种HIV蛋白酶抑制剂。
• [EN] PROCESS FOR MAKING AN EPOXIDE VIA THE IODOHYDRIN<br/>[FR] PROCEDE DE FABRICATION D'UN EPOXYDE PAR L'INTERMEDIAIRE DE L'IODOHYDRINE
  申请人：MERCK & CO., INC.

  公开号：WO1997006164A1

  公开（公告）日：1997-02-20

  (EN) A process for synthesizing the epoxide of formula (I), consists of, at a minimum, formation of a halohydrin from the allyl acetonide reactant, followed by base-induced cyclization, the epoxide product (I) being useful as an intermediate for the synthesis of inhibitors of renin or HIV protease or other proteases.(FR) La présente invention concerne un procédé de synthèse de l'époxyde représenté par la formule: et qui comprend au minimum la formation d'halohydrine à partir du réactant allyle acétonide, suivie de la cyclisation déclenchée par une base. Le produit époxy de formule I est utile comme produit intermédiaire pour la synthèse d'inhibiteurs de la rénine ou de la protéase du VIH ou d'autres protéases.

  一种合成公式（I）的环氧化物的方法，至少包括从烯丙基乙酮酯反应物形成卤代醇，然后通过碱催化环化，公式（I）的环氧化物产物可用作合成抑制剂的中间体，该抑制剂可用于抑制肾素或HIV蛋白酶或其他蛋白酶。（翻译结果）
• Retroviral protease inhibiting compounds
  申请人：——

  公开号：US20010008892A1

  公开（公告）日：2001-07-19

  The present invention discloses novel compounds, compositions, and methods for inhibiting retroviral proteases and in particular for inhibiting human immunodeficiency virus (HIV) protease. The present invention also relates to compositions and methods for treating a retroviral infection and in particular an HIV infection, and to processes for making such compounds and synthetic intermediates employed in these processes.

  本发明揭示了新型化合物、组合物和方法，用于抑制逆转录病毒蛋白酶，特别是用于抑制人类免疫缺陷病毒（HIV）蛋白酶。本发明还涉及用于治疗逆转录病毒感染，特别是HIV感染的组合物和方法，以及用于制备这些化合物和合成中间体的过程。