(S)-1-苯基-1,2,3,4-四氢异喹啉 | 118864-75-8

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: (S)-1-苯基-1,2,3,4-四氢异喹啉
• 中文别名: (S)-1,2,3,4-1-苯基异喹啉；(S)-1,2,3,4-四氢-1-苯基异喹啉；1S-1-苯基-1,2,3,4-四氢异喹啉；索非那新中间体十；(S)1,2,3,4-四氢-1-苯基异喹啉；索非那新中间体 十；S-1-苯基-1,2,3,4-四氢异喹啉
• 英文名称: (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline；1-phenyl-1,2,3,4-tetrahydroisoquinoline；(S)-1-phenyltetrahydroisoquinoline
• CAS: 118864-75-8
• 化学式: C₁₅H₁₅N
• 分子量: 209.291
• InChiKey: PRTRSEDVLBBFJZ-HNNXBMFYSA-N

物化性质

• 熔点：
  80-82°C
• 沸点：
  338°C
• 密度：
  1.065
• 闪点：
  167°C
• 溶解度：
  氯仿（微溶）、二氯甲烷（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2942000000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温下密封保存。

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: (1S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: (1S)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline
CAS number: 118864-75-8

---

Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

---

Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

---

Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

---

Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

---

Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C15H15N
Molecular weight: 209.3

---

Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用 (S)-1-苯基-1,2,3,4-四氢异喹啉可用于制备索非那新。琥珀酸索利那新（Solifenacin Succinate），CAS号为242478-38-2，化学名为1-氮杂双环[2.2.2]辛烷-8-基-(1S)-1-苯基-3,4-二氢-1H-异喹啉-2-甲酸酯丁二酸盐。该药物是日本Astellas公司研发的选择性毒蕈碱M3受体拮抗剂，于2004年首次在荷兰、德国、英国及丹麦上市，并于2009年在中国上市，目前已在全球50多个国家和地区上市销售。琥珀酸索利那新已成为欧洲、美国和日本市场膀胱过度活动症（OAB）治疗的重要药物，获得多个权威机构和指南的推荐。

其制备方法如下：采用(S)-1-苯基-1,2,3,4-四氢异喹啉(I)在有机碱（弱碱条件下与三光气反应缩合得到(S)-1-苯基-3,4-二氢-1H-异喹啉-2-甲酰氯(II)，化合物II不经分离，通过一锅法直接在有机碱催化下加热，与(R)-3-奎宁环醇进行缩合反应，最终得到索利那新(III)，再与琥珀酸成盐制得琥珀酸索利那新(IV)。

合成 将1726毫克L-酒石酸（11.5毫摩尔，1当量）溶解在10毫升甲醇中，然后滴加含有2750毫克（化学纯度87.4%质量分数，11.5毫摩尔）消旋体1-苯基-1,2,3,4-四氢异喹啉的甲醇溶液10毫升。冷却至5℃后，析出晶体。搅拌1小时后减压过滤，除去(R)-1-苯基-1,2,3,4-四氢异喹啉/L-酒石酸盐晶体重结晶后的晶体（R型酒石酸盐）。测定母液中(S)-1-苯基-1,2,3,4-四氢异喹啉S型原料的光学纯度为83%e.e.。向溶液中加入20毫升水，减压蒸馏除去甲醇。然后向得到的溶液（19.65克）中加入30质量％氢氧化钠水溶液调节pH至12，析出晶体。冷却至5℃后搅拌30分钟，再进行减压过滤并用水20毫升清洗。最后，在真空下干燥以获得(S)-1-苯基-1,2,3,4-四氢异喹啉（白色晶体）的S型原料，纯度为93%质量分数，量为1092毫克，摩尔收率为42%，光学纯度82%e.e.。

反应信息

• 作为反应物：
  描述：

  (S)-1-苯基-1,2,3,4-四氢异喹啉 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 37.07h， 生成 2-tert-butyl 1-methyl 1-phenyl-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate
  参考文献：
  名称：

  通过锂化和取代合成 1,1-二取代四氢异喹啉，以及原位红外光谱和构型稳定性研究

  摘要：

  N-Boc-1-苯基四氢异喹啉的锂化通过原位红外光谱优化。测定了氨基甲酸酯基团的旋转动力学和有机锂的对映异构化动力学。有机锂在低温下构型稳定，可以高收率和高对映体比实现1,1-二取代四氢异喹啉的不对称合成。该化学反应用于制备 FR115427，并提供了一种在索利那新合成中回收不需要的对映异构体的方法。

  DOI：

  10.1021/ja500485f
• 作为产物：
  描述：

  2-(2-溴乙基)苯甲醛 在 盐酸 、 sodium hydride 、 copper(II) sulfate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 、 mineral oil 为溶剂， 反应 24.0h， 生成 (S)-1-苯基-1,2,3,4-四氢异喹啉
  参考文献：
  名称：

  Stereoselective Total Syntheses of Solifenacin and N-Acetyl-1-(4-chloro­phenyl)-6,7-dimethoxytetrahydroisoquinoline

  摘要：

  A highly stereoselective synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinoline drugs such as solefinacin (muscarinic acetylcholine receptor antagonist) and N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline (AMPA receptor antagonist) has been accomplished using (R)-tert-butanesulfinamide as a chiral source. Chiral tetrahydroisoquinolines have been prepared through the aryl Grignard addition to chiral N-sulfinylimines followed by haloamide cyclization.

  DOI：

  10.1055/s-0034-1378515

文献信息

• Engineering an Enantioselective Amine Oxidase for the Synthesis of Pharmaceutical Building Blocks and Alkaloid Natural Products
  作者：Diego Ghislieri、Anthony P. Green、Marta Pontini、Simon C. Willies、Ian Rowles、Annika Frank、Gideon Grogan、Nicholas J. Turner

  DOI：10.1021/ja4051235

  日期：2013.7.24

  catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development

  开发用于生产对映异构纯手性胺的经济高效且可持续的催化方法是制药和精细化工行业面临的关键挑战。据估计，40-45% 的候选药物含有手性胺，这突显了这一挑战，这推动了对以高产率和对映体过量提供目标结构的广泛适用的合成方法的需求。在此，我们描述了来自黑曲霉 (MAO-N) 的单胺氧化酶变体“工具箱”的开发和应用，该变体显示出显着的底物范围和对空间要求基序的耐受性，包括一个新变体，它对含有以下物质的底物表现出高活性和对映选择性氨基二苯甲烷（二苯甲基胺）模板。通过将合理的结构导向工程与高通量筛选相结合，可以扩大 MAO-N 的底物范围以适应含有大量芳基取代基的胺底物。这些工程化的 MAO-N 生物催化剂已应用于去消旋反应，用于高效不对称合成仿制药活性药物成分索利那新和左西替利嗪以及天然产物 (R)-coniine、(R)-eleagnine 和 (R)-leptaflorine . 我们还报告了一种新的
• [EN] PROGRANULIN MODULATORS AND METHODS OF USING THE SAME<br/>[FR] MODULATEURS DE PROGRANULINE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ARKUDA THERAPEUTICS

  公开号：WO2019118528A1

  公开（公告）日：2019-06-20

  Provided herein are compounds that modulate progranulin and methods of using the compounds in progranulin-associated disorders, such as Frontotemperal dementia (FTD).

  提供了一种调节颗粒蛋白的化合物及其在颗粒蛋白相关疾病（如额颞叶痴呆（FTD））中的应用方法。
• Safe and Efficient Phosgenation Reactions in a Continuous Flow Reactor
  作者：Hiroaki Yasukouchi、Akira Nishiyama、Masaru Mitsuda

  DOI：10.1021/acs.oprd.7b00353

  日期：2018.2.16

  on the industrial scale is challenging owing to its toxicity. An effective method to minimize reaction volumes and mitigate the safety risks associated with hazardous chemicals is the use of flow reactors. Consequently, we have established a flow reaction system using triphosgene and tributylamine, which affords a homogeneous reaction that avoids clogging issues. In addition, we have demonstrated that

  光气因其高反应性，实用性和成本效益而被广泛用于有机合成中。然而，由于光气的毒性，在工业规模的批量生产中使用光气具有挑战性。最小化反应体积并减轻与危险化学品有关的安全风险的有效方法是使用流动反应器。因此，我们建立了使用三光气和三丁胺的流动反应系统，该系统可提供均相反应，避免发生堵塞问题。另外，我们已经证明，该方法可以良好的收率应用到各种各样的光气反应中，包括制备药物中间体。
• Direct Access to α‐Aminosilanes Enabled by Visible‐Light‐Mediated Multicomponent Radical Cross‐Coupling
  作者：Xiaoye Yu、Constantin G. Daniliuc、Fatmah Ali Alasmary、Armido Studer

  DOI：10.1002/anie.202109252

  日期：2021.10.18

  α-aminosilanes can be obtained in good yields under mild conditions. Both primary amines and secondary amines are compatible with this transformation. Moreover, optically pure α-aminosilanes are accessible by using chiral amines. Mechanistic studies indicate that reactions proceed through radical/radical cross-coupling of silyl radicals with α-amino alkyl radicals.

  α-氨基硅烷是一类具有生物活性的重要有机化合物。在本次交流中，提出了一种α-氨基硅烷的新方法，该方法利用光氧化还原催化使有机（三三甲基硅基）硅烷与原料烷基胺和醛进行三组分偶联。在温和条件下可以以良好的产率获得各种高度官能化的 α-氨基硅烷。伯胺和仲胺都适合这种转变。此外，通过使用手性胺可以获得光学纯的α-氨基硅烷。机理研究表明反应是通过甲硅烷基与α-氨基烷基的自由基/自由基交叉偶联进行的。
• Development of an<i>R</i>-Selective Amine Oxidase with Broad Substrate Specificity and High Enantioselectivity
  作者：Rachel S. Heath、Marta Pontini、Beatrice Bechi、Nicholas J. Turner

  DOI：10.1002/cctc.201301008

  日期：2014.4

  Amine oxidases are useful bio‐catalysts for the synthesis of enantiomerically pure 1°, 2° and 3° chiral amines. Enzymes in this class (e.g., MAO‐N from Aspergillus niger) reported previously have been shown to be highly S selective. Herein we report the development of an enantiocomplementary R‐selective amine oxidase based on 6‐hydroxy‐D‐nicotine oxidase (6‐HDNO) with broadened substrate scope and

  胺氧化酶是用于合成对映体纯的1°，2°和3°手性胺的有用生物催化剂。先前报道的此类酶（例如，来自黑曲霉的MAO-N ）已显示出高度的S选择性。在此，我们报道了基于6-羟基-D-烟碱氧化酶（6-HDNO）的对映体互补R-选择性胺氧化酶的开发，该酶具有扩大的底物范围和高对映选择性。工程化的6-HDNO酶已应用于一系列外消旋胺的制备脱硝反应，以产生具有S构型的产物，例如高ee的（S）-烟碱。