2-甲基-1,2-吲哚啉羧酸-1-叔丁酯 | 186704-03-0

• 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: 2-甲基-1,2-吲哚啉羧酸-1-叔丁酯
• 英文名称: 1-(tert-butyl) 2-methyl indoline-1,2-dicarboxylate
• 英文别名: 1-(Tert-butyl) 2-methyl 1,2-indolinedicarboxylate；1-O-tert-butyl 2-O-methyl 2,3-dihydroindole-1,2-dicarboxylate
• CAS: 186704-03-0
• 化学式: C₁₅H₁₉NO₄
• mdl: MFCD06200867
• 分子量: 277.32
• InChiKey: JWTYDRKOSWALHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338
• 危险性描述：
  H302,H312,H315,H319,H332,H335

SDS

Name:	1-(tert-Butyl) 2-methyl 1 2-indolinedicarboxylate Material Safety Data Sheet
Synonym:	None Known
CAS:	186704-03-0

Section 1 - Chemical Product MSDS Name:1-(tert-Butyl) 2-methyl 1 2-indolinedicarboxylate Material Safety Data Sheet
Synonym:None Known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
186704-03-0	1-(tert-Butyl) 2-methyl 1,2-indolinedi	97+	unlisted

Hazard Symbols: XN
Risk Phrases: 20/21/22 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful by inhalation, in contact with skin and if swallowed.
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation. May cause chemical conjunctivitis.
Skin:
Causes skin irritation. Harmful if absorbed through the skin.
Ingestion:
Harmful if swallowed. May cause irritation of the digestive tract.
Inhalation:
Harmful if inhaled. Causes respiratory tract irritation.
Chronic:
No information found.

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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:
Get medical aid. 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:
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# 186704-03-0: 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: pale-yellow
Odor: odorless
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 73-75 deg C
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: C15H19NO4
Molecular Weight: 277.13

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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:
Dust generation.
Incompatibilities with Other Materials:
Oxidizing agents, acids, bases.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, carbon dioxide.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 186704-03-0 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
1-(tert-Butyl) 2-methyl 1,2-indolinedicarboxylate - 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: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
IMO
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
RID/ADR
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing group: III

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XN
Risk Phrases:
R 20/21/22 Harmful by inhalation, in contact with
skin and if swallowed.
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 22 Do not breathe dust.
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
WGK (Water Danger/Protection)
CAS# 186704-03-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 186704-03-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 186704-03-0 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：

  2-甲基-1,2-吲哚啉羧酸-1-叔丁酯 在 Chirazyme L-2 作用下， 以 phosphate buffer 为溶剂， 反应 30.0h， 生成 methyl (S)-N-(tert-butoxycarbonyl)indoline-2-carboxylate
  参考文献：
  名称：

  Both Enantiomers ofN-Boc-indoline-2-carboxylic Esters

  摘要：

  一种固定化的南极酵母脂肪酶（Chirazyme L-2）催化了N-Boc-吲哚-2-羧酸甲酯的对映选择性水解（E > 1000）。反应在60 °C的温度下高效进行，该温度超过了底物的熔点，反应转化率为49.9%，生成了水解产物(S)-羧酸，其对映体过量纯度（ee）超过99.9%，以及未反应的(R)-酯，其ee为99.6%。从苯胺和乙基α-甲基乙酰乙酸酯出发开发的新型快速路线（共六步，产率60%）建立了所需化合物的可扩展的化学-酶法合成，既可以获得对映体纯度较高的形式。

  DOI：

  10.1246/bcsj.77.1021
• 作为产物：
  描述：

  吲哚-2-羧酸甲酯 在 甲醇 、 4-二甲氨基吡啶 、 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 2-甲基-1,2-吲哚啉羧酸-1-叔丁酯
  参考文献：
  名称：

  Both Enantiomers ofN-Boc-indoline-2-carboxylic Esters

  摘要：

  一种固定化的南极酵母脂肪酶（Chirazyme L-2）催化了N-Boc-吲哚-2-羧酸甲酯的对映选择性水解（E > 1000）。反应在60 °C的温度下高效进行，该温度超过了底物的熔点，反应转化率为49.9%，生成了水解产物(S)-羧酸，其对映体过量纯度（ee）超过99.9%，以及未反应的(R)-酯，其ee为99.6%。从苯胺和乙基α-甲基乙酰乙酸酯出发开发的新型快速路线（共六步，产率60%）建立了所需化合物的可扩展的化学-酶法合成，既可以获得对映体纯度较高的形式。

  DOI：

  10.1246/bcsj.77.1021

文献信息

• Palladium-Catalyzed Reduction of <i>N</i>-(<i>tert</i>-Butoxycarbonyl)indoles by Polymethylhydrosiloxane
  作者：Srivari Chandrasekhar、Debjit Basu、Ch. Raji Reddy

  DOI：10.1055/s-2007-966029

  日期：——

  The palladium-catalyzed [10% Pd(OH)2/C] reduction of N-(tert-butoxycarbonyl)indoles to the corresponding N-(tert-butoxy­carbonyl)indolines is described. Polymethylhydrosiloxane was used as reducing agent and the reaction proceeded smoothly at room temperature in short reaction times giving the products in good yields.

  描述了钯催化（10% Pd(OH)2/C）还原N-叔丁氧羰基吲哚为相应N-叔丁氧羰基二氢吲哚的过程。使用聚甲基氢硅氧烷作为还原剂，在室温下短时间内反应顺利进行，产率良好。
• [EN] SPIROCYCLOHEPTANES AS INHIBITORS OF ROCK<br/>[FR] SPIROCYCLOHEPTANES UTILISÉS EN TANT QU'INHIBITEURS DE ROCK
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016010950A1

  公开（公告）日：2016-01-21

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically-acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

  本发明提供了式(I)的化合物：或立体异构体、互变异构体或药用可接受的盐，其中所有变量均如本文所述定义。这些化合物是选择性的ROCK抑制剂。本发明还涉及包含这些化合物的药物组合物，以及使用同一化合物治疗心血管、平滑肌、肿瘤学、神经病理学、自身免疫、纤维化和/或炎症性疾病的方法。
• Orthogonal Synthesis of Indolines and Isoquinolines via Aryne Annulation
  作者：Christopher D. Gilmore、Kevin M. Allan、Brian M. Stoltz

  DOI：10.1021/ja0780582

  日期：2008.2.6

  exploiting the reactivity of arynes. Reaction of N-carbamoyl-functionalized enamine derivatives with benzyne affords substituted indolines. An orthogonal reactivity is uncovered when related enamine derivatives are modified as amides, such that isoquinolines are formed as the product of condensation with benzyne. This latter transformation is applied to a concise total synthesis of the opiate alkaloid papaverine

  本报告中描述了两种利用芳炔反应性的独特方法的发展。N-氨基甲酰基官能化的烯胺衍生物与苄的反应提供取代的二氢吲哚。当相关的烯胺衍生物被修饰为酰胺时，就会发现正交反应性，这样异喹啉就可以作为与苄缩合的产物形成。后一种转化适用于鸦片生物碱罂粟碱的简明全合成。
• Hexafluoroisopropanol: a powerful solvent for the hydrogenation of indole derivatives. Selective access to tetrahydroindoles or cis-fused octahydroindoles
  作者：Damien Clarisse、Bernard Fenet、Fabienne Fache

  DOI：10.1039/c2ob25980j

  日期：——

  Pd/C in HFIP was used to hydrogenate indole derivatives under relatively mild conditions, leading to potential synthetic intermediates of bioactive compounds. Depending on their substitution, tetrahydroindoles or octahydroindoles could selectively be obtained.

  HFIP中的Pd / C用于在相对温和的条件下氢化吲哚衍生物，从而导致潜在的生物活性化合物的合成中间体。根据它们的取代，可以选择性地获得四氢吲哚或八氢吲哚。
• Electrochemical Dearomative Dicarboxylation of Heterocycles with Highly Negative Reduction Potentials
  作者：Yong You、Wataru Kanna、Hideaki Takano、Hiroki Hayashi、Satoshi Maeda、Tsuyoshi Mita

  DOI：10.1021/jacs.1c13032

  日期：2022.3.2

  CO2 radical anion (E1/2 of CO2 = −2.2 V in DMF and −2.3 V in CH3CN vs SCE) that produces unprecedented trans-oriented 2,3-dicarboxylic acids from N-Ac-, Boc-, and Ph-protected indoles that exhibit highly negative reduction potentials (−2.50 to −2.94 V). On the basis of the calculated reduction potentials, N-protected indoles with reduction potentials up to −3 V smoothly undergo the desired dicarboxylation

  使用 CO 2对稳定的杂芳烃进行脱芳族二羧基化具有很高的挑战性，但它代表了一种非常有效的生产合成有用二羧酸的方法，二羧酸有可能用作生物活性分子（如天然产物和药物先导物）的中间体。然而，这些类型的转化仍然不发达，高效的简明方法（例如，高产率和高选择性的二羧基化）尚未见报道。我们在此描述了一种使用 CO 2自由基阴离子（ DMF 中的E 1/2的 CO 2 = -2.2 V 和 CH 3 CN vs SCE 中的 -2.3 V）的新电化学方案，该方案产生前所未有的反式来自N -Ac-、Boc- 和 Ph-保护的吲哚的取向 2,3-二羧酸，具有高负还原电位（-2.50 至 -2.94 V）。基于计算的还原电位，还原电位高达-3 V的N-保护吲哚顺利地进行了所需的二羧化。其他杂芳烃，包括苯并呋喃、苯并噻吩、缺电子呋喃、噻吩、1,3-二苯基异苯并呋喃和N-Boc-吡唑，也表现出比 -3 V 更正的还