(S)-indoline 2-carboxylic acid methyl ester hydrochloride | 96056-64-3

• 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
• 英文名称: (S)-indoline 2-carboxylic acid methyl ester hydrochloride
• 英文别名: methyl indoline-2-carboxylate hydrochloride；(2S)-methyl indoline-2-carboxylate hydrochloride；indoline-2-carboxylic acid methyl ester hydrochloride；methyl 2,3-dihydro-1H-indole-2-carboxylate hydrochloride；methyl 2,3-dihydro-1H-indole-2-carboxylate;hydrochloride
• CAS: 96056-64-3
• 化学式: C₁₀H₁₁NO₂*ClH
• 分子量: 213.664
• InChiKey: FEJNUJIJMMGHMS-UHFFFAOYSA-N

物化性质

• 熔点：
  117℃

计算性质

• 辛醇/水分配系数(LogP)：
  1.62
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S25,S26,S36/37
• 危险类别码：
  R62,R48/22,R43
• 海关编码：
  2933990090
• 储存条件：
  存储条件：2-8°C，密封，干燥。

SDS

Name:	Methyl 2-indolinecarboxylate Material Safety Data Sheet
Synonym:	None Known
CAS:	96056-64-3

Section 1 - Chemical Product MSDS Name:Methyl 2-indolinecarboxylate Material Safety Data Sheet
Synonym:None Known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
96056-64-3	Methyl 2-indolinecarboxylate	95+	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 gastrointestinal irritation with nausea, vomiting and diarrhea.
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:
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.
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 appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Absorb spill with inert material (e.g. vermiculite, sand or earth), then place in suitable container. Avoid runoff into storm sewers and ditches which lead to waterways. Clean up spills immediately, observing precautions in the Protective Equipment section. Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
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 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# 96056-64-3: 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:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Liquid
Color: pale yellow
Odor: odorless
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: C10H11NO2
Molecular Weight: 177.20

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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.
Incompatibilities with Other Materials:
Acids, bases, oxidizing agents.
Hazardous Decomposition Products:
Hydrogen chloride, nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 96056-64-3 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Methyl 2-indolinecarboxylate - 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 LIQUID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2810
Packing Group: III
IMO
Shipping Name: TOXIC LIQUID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2810
Packing Group: III
RID/ADR
Shipping Name: TOXIC LIQUID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2810
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 23 Do not inhale gas/fumes/vapour/spray.
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.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 96056-64-3: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 96056-64-3 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 96056-64-3 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：

  (S)-indoline 2-carboxylic acid methyl ester hydrochloride 在 [rhodium(I)(norborna-2,5-diene)2]SbF₆ 4-二甲氨基吡啶 、 chiral ferrocene-based 、 氢气 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 异丙醇 、 甲苯 为溶剂， 20.0~100.0 ℃ 、10.13 MPa 条件下， 反应 24.5h， 生成 (S)-1-乙酰基二氢吲哚-2-羧酸甲酯
  参考文献：
  名称：

  铑配合物与手性双膦配体PhTRAP的吲哚催化不对称加氢

  摘要：

  通过使用由[Rh（nbd）2 ] SbF 6原位生成的铑催化剂和手性双膦PhTRAP，可以成功地开发出N-保护的吲哚的高度对映选择性氢化反应，可以与过渡金属原子形成反式-螯合物。PhTRAP-铑催化剂需要碱（例如Cs 2 CO 3）才能实现高对映选择性。将各种2-取代的N-乙酰吲哚转化为具有高达95％ee的相应的手性二氢吲哚。3-取代的N - tosylindoles的氢化产生二氢吲哚，其在3-位具有立体异构中心，具有高的对映异构体过量（至多98％ee）。

  DOI：

  10.1016/j.tetasy.2006.01.016
• 作为产物：
  描述：

  甲醇 、 吲哚啉-2-羧酸 在 氯化亚砜 作用下， 以91%的产率得到(S)-indoline 2-carboxylic acid methyl ester hydrochloride
  参考文献：
  名称：

  铑配合物与手性双膦配体PhTRAP的吲哚催化不对称加氢

  摘要：

  通过使用由[Rh（nbd）2 ] SbF 6原位生成的铑催化剂和手性双膦PhTRAP，可以成功地开发出N-保护的吲哚的高度对映选择性氢化反应，可以与过渡金属原子形成反式-螯合物。PhTRAP-铑催化剂需要碱（例如Cs 2 CO 3）才能实现高对映选择性。将各种2-取代的N-乙酰吲哚转化为具有高达95％ee的相应的手性二氢吲哚。3-取代的N - tosylindoles的氢化产生二氢吲哚，其在3-位具有立体异构中心，具有高的对映异构体过量（至多98％ee）。

  DOI：

  10.1016/j.tetasy.2006.01.016

文献信息

• Dithiolan derivatives, their preparation and their therapeutic effect
  申请人：Sankyo Company, Limited

  公开号：US06013663A1

  公开（公告）日：2000-01-11

  A compound of formula (I): ##STR1## wherein one of m and n represents 0, and the other represents 0, 1 or 2; k represents 0 or 1 to 12; R.sup.1 is hydrogen, an aryl, a heterocyclic, an alkyl, a hydroxy or --OR.sup.7, wherein R.sup.7 is an alkyl, an alkenyl or an aralkyl; A is --CON(R.sup.2)SO.sub.2--, wherein R.sup.2 is hydrogen, an alkyl or an aralkyl; B is a single bond; and pharmaceutically acceptable salts thereof. The compounds have the ability to enhance the activity of glutathione reductase and can therefore be used for the treatment and prevention of a variety of diseases including cataracts.

  式（I）的化合物：其中m和n中的一个表示0，另一个表示0、1或2；k表示0或1至12；R.sup.1是氢、芳基、杂环、烷基、羟基或--OR.sup.7，其中R.sup.7是烷基、烯基或芳基烷基；A是--CON(R.sup.2)SO.sub.2--，其中R.sup.2是氢、烷基或芳基烷基；B是单键；以及其药学上可接受的盐。这些化合物具有增强谷胱甘肽还原酶活性的能力，因此可用于治疗和预防包括白内障在内的各种疾病。
• Spiropiperidine compounds as ligands for ORL-1 receptor
  申请人：Pfizer Inc.

  公开号：US20030078278A1

  公开（公告）日：2003-04-24

  A compound of the formula: 1 or a salt, prodrug or solvate thereof, wherein R 1 and R 2 groups are all hydrogen; A is a benzofuzed azahetero ring; W 1 —W 2 is CH 2 —CH 2 ; X 1 —X 2 is CH 2 —CH 2 ; and Z is methylene or carbonyl; or the like, is a ligand for ORL1-receptor and are useful for treating or preventing pain, a CNS disorder or the like in mammalian subjects.

  该公式的化合物：1或其盐、前药或溶剂，其中R1和R2基团均为氢；A为苯并噻杂环；W1-W2为CH2-CH2；X1-X2为CH2-CH2；Z为亚甲基或羰基；或类似物，是ORL1受体的配体，可用于治疗或预防哺乳动物主体中的疼痛、中枢神经系统紊乱或类似疾病。
• [EN] METHOD FOR PREPARING (S)-INDOLINE-2-CARBOXYLIC ACID AND (S)-INDOLINE-2-CARBOXYLIC ACID METHYL ESTER USING HYDROLYTIC ENZYME<br/>[FR] METHODE DE PREPARATION D'UN ACIDE CARBOXYLIQUE (S)-INDOLINE-2 ET D'UN ESTER DE METHYLE D'ACIDE CARBOXYLIQUE (S)-INDOLINE-2 A L'AIDE D'UNE ENZYME HYDROLYTIQUE
  申请人：SK CORP

  公开号：WO2005051910A1

  公开（公告）日：2005-06-09

  Disclosed is a method for preparing (S)-indoline-2-carboxylic acid and (S)-indoline-2-carboxylic acid methyl ester using an inexpensive industrially available enzyme capable of assuring superior optical purity and yield. At this time, the hydrolytic enzyme is selected from the group consisting of Savinase, Alcalase, Novozym 243, Everlase, Esperase, Protease 7 and Acylase, whereby (S)-indoline-2-carboxylic acid and methyl ester thereof having an optical purity of at least 99%e.e. can be obtained through a simplified preparation process, thus generating economic benefits.

  本发明公开了一种使用廉价工业可得酶制备（S）-吲哚-2-羧酸和（S）-吲哚-2-羧酸甲酯的方法，该方法能够保证卓越的光学纯度和产率。在此时，水解酶被选择自Savinase，Alcalase，Novozym 243，Everlase，Esperase，Protease 7和Acylase等组中，通过简化的制备过程，可以获得具有至少99%e.e.的光学纯度的（S）-吲哚-2-羧酸和其甲酯，从而产生经济效益。
• [EN] ANTIHYPERTENSIVE TRICYCLIC AZEPINE DERIVATIVES USEFUL AS INHIBITORS OF ENKEPHALINASE AND ACE<br/>[FR] DERIVES D'AZEPINE TRICYCLIQUES ANTIHYPERTENSION UTILISES COMME INHIBITEURS D'ENCEPHALINASE ET D'ACE
  申请人：CIBA-GEIGY AG

  公开号：WO1995001353A1

  公开（公告）日：1995-01-12

  (EN) Disclosed are the tricyclic azepine derivatives of formula (I) wherein X represents oxo, one hydroxy or lower alkoxy and one hydrogen, or two hydrogens; Ra and Rb independently represent hydrogen, hydroxy, lower alkoxy, nitro, amino or halogen; or Ra and Rb on adjacent carbons taken together represent lower alkylenedioxy; Rc represents hydrogen, lower alkyl or aryl-lower alkyl; R represents hydrogen or acyl; R1 represents hydrogen, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, biaryl, biaryl-lower alkyl or trifluoromethyl; R2 represents hydrogen or lower alkyl; or R1 and R2 together with the carbon to which they are attached represent cycloalkylene or benzo-fused cycloalkylene; m represents one or two; n represents zero or one; COOR3 represents carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester; disulfide derivatives formed from said compounds wherein R is hydrogen; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; methods for preparation of said compounds; intermediates; and methods of treating disorders in mammals which are responsive to ACE and NEP inhibition by administration of said compounds to mammals in need of such treatment.(FR) L'invention se rapporte aux dérivés d'azépine tricycliques de la formule (I), dans laquelle X représente oxo, un hydroxy ou un alcoxy inférieur et un hydrogène ou deux hydrogènes; Ra et Rb représentent indépendamment hydrogène, hydroxy, alcoxy inférieur, nitro, amino ou halogène; ou Ra et Rb sur des atomes de carbone adjacents représentent ensemble alkylènedioxy inférieur; Rc représente hydrogène, alkyle inférieur ou aryl-alkyle inférieur; R représente hydrogène ou acyle; R1 représente hydrogène, alkyle inférieur, aryle, aryl-alkyle inférieur, cycloalkyl-alkyle inférieur, biaryle, biaryl-alkyle inférieur ou trifluorométhyle; R2 représente hydrogène ou alkyle inférieur; ou R1 et R2 représentent, avec l'atome de carbone auquel ils sont rattachés, cycloalkylène ou cycloalkylène benzofusionnés; m représente un ou deux; n représente zéro ou un; COOR3 représente carboxyle ou carboxyle dérivé sous forme d'un ester pharmaceutiquement aceptable. L'invention se rapporte également à des dérivés bisulfurés formés à partir desdits composés, R représentant hydrogène; à leurs sels pharmaceutiquement acceptables; à des compositions pharmaceutiques comprenant lesdits composés; à des procédés de préparation desdits composés; à des intermédiaires; ainsi qu'à des procédés de traitement d'affections, chez les mammifères, qui réagissent à l'inhibition de l'enzyme de conversion d'angiotensine (ACE) et de l'endopeptidase neutre (NEP), consistant à administrer ces composés aux mammifères nécessitant un tel traitement.

  (中) 本发明涉及式(I)中的三环氮杂环衍生物，其中X表示氧代、一个羟基或低级烷氧基和一个氢原子，或两个氢原子；Ra和Rb分别表示氢原子、羟基、低级烷氧基、硝基、氨基或卤素；或者Ra和Rb在相邻的碳原子上结合成为低级亚烷基二氧化物；Rc表示氢原子、低级烷基或芳基-低级烷基；R表示氢原子或酰基；R1表示氢原子、低级烷基、芳基、芳基-低级烷基、环烷基、环烷基-低级烷基、双芳基、双芳基-低级烷基或三氟甲基；R2表示氢原子或低级烷基；或者R1和R2与它们所连接的碳原子共同表示环烷基或苯并环烷基；m表示1或2；n表示0或1；COOR3表示羧基或以药学上可接受的酯形式衍生的羧基；以及由该化合物形成的二硫化物衍生物，其中R为氢原子；以及其药学上可接受的盐；包含该化合物的制药组合物；制备该化合物的方法；中间体；以及通过向需要该治疗的哺乳动物投药该化合物来治疗对ACE和NEP抑制有反应的哺乳动物的疾病的方法。
• Spiropiperidine compounds as ligands for ORL-1receptor
  申请人：Pfizer Inc.

  公开号：US20030078279A1

  公开（公告）日：2003-04-24

  A compound of the formula: 1 or a salt, prodrug or solvate thereof, wherein R 1 and R 2 groups are all hydrogen; A is a benzofuzed azahetero ring; W 1 -W 2 is CH 2 -CH 2 ; X 1 -X 2 is CH 2 -CH 2 ; and Z is methylene or carbonyl; or the like, is a ligand for ORL1-receptor and are useful for treating or preventing pain, a CNS disorder or the like in mammalian subjects.

  式中的化合物： 1 或其盐、原药或溶液，其中 R 1 和 R 2 基团均为氢；A 为苯并偶氮杂环；W 1 -W 2 是 CH 2 -CH 2 ; X 1 -X 2 是 CH 2 -CH 2 和 Z 是亚甲基或羰基；或类似物，是 ORL1 受体的配体，可用于治疗或预防哺乳动物的疼痛、中枢神经系统疾病或类似疾病。