3-溴-1-金刚烷甲酸 | 21816-08-0

• 物质功能分类: 化学试剂 - 手性化学试剂
• 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: 3-溴-1-金刚烷甲酸
• 中文别名: 3-溴金刚烷-1-甲酸；1-溴-3-金刚烷甲酸；3-溴金刚烷-1-羧酸
• 英文名称: 3-bromoadamantane-1-carboxylic acid
• 英文别名: 3-bromo-1-adamantanecarboxylic acid；3-Bromadamantan-1-carbonsaeure
• CAS: 21816-08-0
• 化学式: C₁₁H₁₅BrO₂
• mdl: MFCD00167820
• 分子量: 259.143
• InChiKey: DJUDQBVINJIMFO-UHFFFAOYSA-N

物化性质

• 熔点：
  147 °C
• 沸点：
  354.2±25.0 °C(Predicted)
• 密度：
  1.665±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.909
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26,S37/39
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• RTECS号：
  AU4452500
• 海关编码：
  2916209090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C

SDS

Name:	3-Bromoadamantane-1-carboxylic acid 97% Material Safety Data Sheet
Synonym:
CAS:	21816-08-0

Section 1 - Chemical Product MSDS Name:3-Bromoadamantane-1-carboxylic acid 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
21816-08-0	3-Bromoadamantane-1-carboxylic acid	97%	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.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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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.
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.
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.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
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# 21816-08-0: Personal Protective Equipment Eyes: Not available.
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
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 143 - 145 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: C11H15BrO2
Molecular Weight: 259

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, carbon dioxide, hydrogen bromide, acrid smoke and fumes, bromine.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 21816-08-0: AU4452500 LD50/LC50:
Not available.
Carcinogenicity:
3-Bromoadamantane-1-carboxylic acid - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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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
No information available.
IMO
No information available.
RID/ADR
No information available.

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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# 21816-08-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 21816-08-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 21816-08-0 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

制备方法与用途

应用

3-溴-1-金刚烷甲酸是一种有机中间体，可通过将金刚烷甲酸进行溴代制备得到。金刚烷及其衍生物在医药领域可用于制造各种特效药物。

制备

向液溴中缓慢添加金刚烷甲酸，并在无水三氯化铝的催化作用下，先于20℃至10℃温度下搅拌回流反应48-60小时，再将温度调整至20℃至30℃条件下继续反应5小时。最终可合成得到3-溴-1-金刚烷甲酸。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  1-金刚烷甲酸	1-Adamantanecarboxylic acid	828-51-3	C11H16O2	180.247

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	1-bromo-3-methoxycarbonyladamantane	27983-08-0	C12H17BrO2	273.17
  ——	(3-bromotricyclo[3.3.1.13,7]dec-1-yl)methanol	36964-33-7	C11H17BrO	245.159
  1,3-金刚烷二甲酸	adamantane-1,3-dicarboxylic acid	39269-10-8	C12H16O4	224.257
  3-溴-金刚烷-1-甲酰氯	3-bromo-1-adamantanecarbonyl chloride	39917-36-7	C11H14BrClO	277.589
  3-溴-1-金刚烷甲酰胺	1-bromo-3-carboxamidoadamantane	53263-89-1	C11H16BrNO	258.158

反应信息

• 作为反应物：
  描述：

  3-溴-1-金刚烷甲酸 在 (trimethylstannyl)lithium 、 2-碘-1,1,1-三氟乙烷 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 苯 为溶剂， 反应 0.5h， 生成 金刚烷
  参考文献：
  名称：

  Mechanistic definition of trimethylstannylation of 1,3-dihaloadamantanes: delocalized radical anions as possible intermediates

  摘要：

  A series of 1,3-dihaloadamantanes (3, X = Y = halogens) have been synthesized, characterized, and treated with (trimethylstannyl) alkali reagents (Me3SnM, M = Li or Na) in the absence and presence of tert-butylamine (TBA) and dicyclohexylphosphine (DCPH). The product distributions of these reactions have been established by C-13 and Sn-119 NMR spectroscopy and vapor-phase chromatographic analyses. Tin substitution via an S(RN)1-type pathway is shown to be a significant reaction for several of the derivatives of 3 (X = F, Y Br or I; X = Cl, Y = Br or I; X = Y = Br) but not for the bromo iodide or diiodide (3, X = Br, Y = I and X = Y = I). For the latter two compounds, the formation of 1,3-dehydroadamantane or propellane 8 is the predominant reaction product while tin substitution is insignificant. Propellane 8 formation is also a significant reaction product for some of the other dihalo derivatives of 3 (X = Cl, Y = I and X = Y = Br) but not for others (3, X = F, Y = Br or I and X = Cl, Y = Br). The mechanism of formation of 8 is perplexing in light of the trapping experiments in the presence of TBA and DCPH. A possible pathway is proposed in which the key intermediate is a delocalized radical anion.

  DOI：

  10.1021/jo00078a009
• 作为产物：
  描述：

  1-金刚烷甲酸 在 硫酸 、 氢溴酸 、 硝酸 作用下， 以 水 为溶剂， 反应 9.5h， 生成 3-溴-1-金刚烷甲酸
  参考文献：
  名称：

  用于生物共轭的叠氮基-金刚烷基锡硫化物簇。

  摘要：

  我们为生物分子功能化的硫化锡簇提出了一条新的通用路线。开发了一种新型的双功能正交间隔基，并将其用于形成三折叠氮基-金刚烷基末端的簇，作为点击反应的基础。叠氮基簇通过菌株促进的1，3-偶极环加成被定量生物缀合，从而提供了肽修饰的簇。

  DOI：

  10.1021/acs.organomet.8b00734

文献信息

• ANTI-EGFR ANTIBODY DRUG CONJUGATES
  申请人：AbbVie Inc.

  公开号：US20190153107A1

  公开（公告）日：2019-05-23

  The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.

  这项发明涉及抑制Bcl-xL的抗表皮生长因子受体（EGFR）抗体药物结合物（ADCs），包括使用所述ADCs的组合物和方法。
• Modular synthesis of bis- and tris-1,2,3-triazoles by permutable sequential azide–aryne and azide–alkyne cycloadditions
  作者：Suguru Yoshida、Takako Nonaka、Takamoto Morita、Takamitsu Hosoya

  DOI：10.1039/c4ob01654h

  日期：——

  the basis of sequential azide–aryne and azide–alkyne cycloadditions. The key to success was efficient halogen–metal exchange reaction-mediated generation of aryne from ortho-iodoaryl triflates bearing a base-sensitive terminal alkyne moiety, which was achieved using trimethylsilylmethyl Grignard reagent.

  在顺序叠氮化物-芳烃和叠氮化合物-炔烃环加成反应的基础上，开发了包括苯并三唑结构在内的双-和三-1,2,3-三唑的模块化合成方法。成功的关键是由卤素-金属交换反应介导的从带有碱敏性末端炔基部分的邻碘代芳基三氟甲磺酸酯生成芳烃，这是使用三甲基甲硅烷基甲基格氏试剂实现的。
• [EN] ANTIBODY DRUG CONJUGATES WITH CELL PERMEABLE BCL-XL INHIBITORS<br/>[FR] CONJUGUÉS ANTICORPS MÉDICAMENTS AVEC DES INHIBITEURS BCL-XL À PERMÉABILITÉ CELLULAIRE
  申请人：ABBVIE INC

  公开号：WO2016094505A1

  公开（公告）日：2016-06-16

  Small molecule Bcl-xL inhibitors and Antibody Drug Conjugates (ADCs) comprising small molecule Bcl-xL inhibitors are disclosed herein. The Bcl-xL inhibitors and ADCs of the disclosure are useful for, among other things, inhibiting anti-apoptotic Bcl xL proteins as a therapeutic approach towards the treatment of diseases that involve a dysregulated apoptosis pathway.

  本文披露了小分子Bcl-xL抑制剂和包含小分子Bcl-xL抑制剂的抗体药物结合物（ADCs）。本公开的Bcl-xL抑制剂和ADCs可用于抑制抗凋亡Bcl-xL蛋白，作为治疗涉及失调凋亡途径的疾病的治疗方法之一。
• [EN] 6,7-DIHYDRO-5H-PYRIDO[2,3-C]PYRIDAZINE DERIVATIVES AND RELATED COMPOUNDS AS BCL-XL PROTEIN INHIBITORS AND PRO-APOPTOTIC AGENTS FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE 6,7-DIHYDRO-5H-PYRIDO[2,3-C]PYRIDAZINE ET COMPOSÉS APPARENTÉS EN TANT QU'INHIBITEURS DE PROTÉINE BCL-XL ET AGENTS PRO-APOPTOTIQUES POUR LE TRAITEMENT DU CANCER
  申请人：SERVIER LAB

  公开号：WO2021018858A1

  公开（公告）日：2021-02-04

  The present invention discloses 6,7-dihydro-5H-pyrido[2,3- c]pyridazine, 1,2,3,4-tetrahydroquinoline, 1H-indole, 3,4- dihydro-2H-1,4-benzoxazine, 1H-pyrrolo[2,3-b]pyridin-1-yl, 7H- pyrrolo[2,3-c]pyridazine, 5H,6H,7H,8H,9H-pyridazino[3,4-b]azepine derivatives and related compounds of formula (I) as Bcl-xL protein inhibitors for use as pro-apoptotic agents for treating cancer, autoimmune diseases or immune system diseases. Formula (I). The description discloses the preparation of exemplary compounds (e.g. pages 113 to 354 examples 1 to 221) as well as pharmacological studies with relevant data (e.g. pages 355 to 367; examples A to E; tables 1 to 5). Exemplary compounds are e.g. 2-6-[(1,3-benzothiazol-2-yl) amino]-1,2,3,4-tetrahydroquinolin-1-yl}-1,3-thiazole-4-carboxylic acid (example 1) or e.g. 3-1-[(adamantan-1-yl)methyl]-5- methyl-1H-pyrazol-4-yl}-6-3-[(1,3-benzothiazol-2-yl)amino]-4- methyl-5H,6H,7H,8H-pyrido[2,3-c]pyridazin-8-yl]pyridine-2-carboxylic acid (example 24).

  本发明公开了作为Bcl-xL蛋白抑制剂用于治疗癌症、自身免疫疾病或免疫系统疾病的促凋亡剂的6,7-二氢-5H-吡啶并[2,3-c]吡啶嗪、1,2,3,4-四氢喹啉、1H-吲哚、3,4-二氢-2H-1,4-苯并噁嗪、1H-吡咯并[2,3-b]吡啶-1-基、7H-吡咯并[2,3-c]吡啶嗪、5H,6H,7H,8H,9H-吡啶并[3,4-b]氮杂环庚烷衍生物和相关化合物的化学式(I)。描述了示例化合物的制备（例如第113至354页的示例1至221）以及具有相关数据的药理学研究（例如第355至367页；示例A至E；表1至5）。示例化合物包括例如2-6-[(1,3-苯并噻唑-2-基)氨基]-1,2,3,4-四氢喹啉-1-基}-1,3-噻唑-4-羧酸（示例1）或例如3-1-[(1-金刚烷-1-基)甲基]-5-甲基-1H-吡唑-4-基}-6-3-[(1,3-苯并噻唑-2-基)氨基]-4-甲基-5H,6H,7H,8H-吡啶并[2,3-c]吡啶-8-基]吡啶-2-羧酸（示例24）。
• Zinc-Mediated Decarboxylative Alkylation of <i>Gem</i>-difluoroalkenes
  作者：Liting Yu、Mei-Lin Tang、Chang-Mei Si、Zhi Meng、Yongxi Liang、Jilai Han、Xun Sun

  DOI：10.1021/acs.orglett.8b01866

  日期：2018.8.3

  An efficient and mild zinc-mediated decarboxylative alkylation of gem-difluoroalkenes with N-hydroxyphthalimide (NHP) esters, to give monofluoroalkenes in moderate to excellent yields with high Z-selectivity is reported. The reaction tolerates a broad range of functional groups and can be easily scaled up, which thus may pave the way for its further applications in medicinal chemistry and materials

  据报道，用N-羟基邻苯二甲酰亚胺（NHP）酯对宝石-二氟烯烃进行了有效且温和的锌介导的脱羧烷基化，以中等至优异的收率和高Z选择性得到了单氟烯烃。该反应可耐受各种官能团，并且可以轻松按比例放大，因此可为其在药物化学和材料科学中的进一步应用铺平道路。