(S)-(-)-1,2,3,4-四氢-3-异喹啉羧酸苄酯 对甲苯磺酸盐 | 77497-97-3

• 物质功能分类: 化学试剂 - 有机试剂
• 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: (S)-(-)-1,2,3,4-四氢-3-异喹啉羧酸苄酯 对甲苯磺酸盐
• 中文别名: (S)-(-)-1,2,3,4-四氢-3-异喹啉羧酸苄酯对甲苯磺酸盐；(S)-(-)-1,2,3,4-四氢-3-异喹啉甲酸苄酯对甲苯磺酸盐；(S)-1,2,3,4-四氢-3-异喹啉羧酸苄酯对甲苯磺酸盐；(3S)-1,2,3,4-四氢异喹啉-羧酸苄酯对甲苯磺酸盐
• 英文名称: benzyl (S)-(-)-1,2,3,4-tetrahydro-3-isoquinoline carboxylate p-toluenesulfonic acid salt
• 英文别名: benzyl (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate p-toluenesulfonate；4-toluenesulfonic acid benzyl (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate；(S)-benzyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate p-toluenesulfonic acid salt；(S)-benzyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate p-toluenesulfonic acid；para-toluene sulfonate salt of the benzyl ester of (S)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid；(S)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, phenylmethyl ester tosylate salt；benzyl (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate tosylate；(3S)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid phenylmethyl ester 4-methylbenzenesulfonate (1:1)；benzyl (3S)-1,2,3,4-tetrahydroisoquinolin-2-ium-3-carboxylate;4-methylbenzenesulfonate
• CAS: 77497-97-3
• 化学式: C₇H₈O₃S*C₁₇H₁₇NO₂
• 分子量: 439.532
• InChiKey: PSMBIFNNFMRIMV-NTISSMGPSA-N

物化性质

• 熔点：
  145-150°C

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险品标志：
  N
• 危险类别码：
  R51/53
• 危险品运输编号：
  UN 3077
• 海关编码：
  2933499090
• 安全说明：
  S61
• WGK Germany：
  2
• 包装等级：
  III
• 危险类别：
  9
• 危险性防范说明：
  P201,P264,P280,P301+P330+P331,P312
• 危险性描述：
  H302,H361,H372,H410

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Benzyl (s)-(-)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate p-toluenesulfonic acid salt
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H411: Toxic to aquatic life with long lasting effects
P273: Avoid release to the environment

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Section 3. Composition/information on ingredients.
Ingredient name: Benzyl (s)-(-)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate p-toluenesulfonic acid salt
CAS number: 77497-97-3

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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.

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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.

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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.

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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.
Storage: Store in closed vessels.

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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.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C17H17NO2.C7H8O3S
Molecular weight: 439.5

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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, sulfur oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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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.

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

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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.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (S)-(-)-1,2,3,4-四氢-3-异喹啉羧酸苄酯 对甲苯磺酸盐 在 4-二甲氨基吡啶 、 5%-palladium/activated carbon 、 氢气 、 碳酸氢钠 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 25.0 ℃ 、5.0 kPa 条件下， 反应 31.0h， 生成 (S)-N-[(4-methylphenyl)sulfonyl]-2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Synthesis and Characterization of N-Substituted (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxamides and Thioamides as Organocatalysts for Asymmetric Aldol Reaction

  摘要：

  DOI：

  10.3987/com-14-13029
• 作为产物：
  描述：

  L-苯丙氨酸 在 盐酸 作用下， 以 水 、 苯 为溶剂， 反应 9.0h， 生成 (S)-(-)-1,2,3,4-四氢-3-异喹啉羧酸苄酯 对甲苯磺酸盐
  参考文献：
  名称：

  Facile Preparation of optically Pure (3S)- and (3R)- 1, 2, 3, 4-Tetrahydroisoquinoline-3-carboxylic Acid

  摘要：

  光学纯的(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸(1)通过对其苄基酯(2b)的分馏结晶法轻松获得，该苄基酯是由部分消旋的1盐酸盐制备而成，随后经过催化去苄基化。同样，(3R)-1也是通过相同的程序制备的。在使用光学活性的苯丙氨酸进行Pictet-Spengler反应时，通过在存在手性位移试剂的情况下，对反应产物(1)所得到的相应甲基酯(2a)进行1H核磁共振(1H-NMR)光谱分析，确定了消旋化的程度。

  DOI：

  10.1248/cpb.31.312

文献信息

• [EN] CRYSTALLINE FORM OF QUINAPRIL HYDROCHLORIDE AND PROCESS FOR PREPARING THE SAME<br/>[FR] FORME CRISTALLINE D'UN HYDROCHLORURE DE QUINAPRIL ET PROCEDE DE PREPARATION DE CELLE-CI
  申请人：LUPIN LTD

  公开号：WO2004054980A1

  公开（公告）日：2004-07-01

  A novel crystalline form of quinapril hydrochloride of formula (I). An amorphous form of quinapril hydrochloride substantially free of impurities, specially diketopiperazine compound, and conforming to pharmacopoeial specifications formed from the said novel crystalline form of quinapril hydrochloride of formula (I). The crystalline quinapril hydrochloride is in the form nitroalkane solvate in which the nitroalkane is nitromethane, nitroethane and nitropropane. Each such nitroalkane solvate having particular characteristic X- ray diffraction patterns. A process for preparation of amorphous from of quinapril hydrochloride, substantially free of impurities, specially diketopiperazine compound, and conforming to pharmacopoeial specifications, using the novel crystalline quinapril hydrochloride as an intermediate. The process involves obtaining free base compound of formula (V) by adjusting the pH of a solution of the benzyl ester maleate salt of quinapril of formula (V) between 7.5-8.5 in a mixture of water and an organic solvent; catalytic hydrogenation of this compound (V) in an alcoholic solvent in the presence of concentrated hydrochloric acid or hydrogen chloride dissolved in an alcoholic solvent and in the presence of catalytic amounts of Pd/C to obtain a residue containing formula (I); crystallization of the said residue by evaporating the alcoholic solvent from a nitroalkane solvent to give crystalline quinapril hydrochloride, associated with a solvate of the nitroalkane solvent, and drying the crystalline quinapril hydrochloride nitroalkane solvate at a temperature between 40°C and 45°C under vacuum to give amorphous quinapril hydrochloride of formula (I).

  盐酸喹那普利的一种新颖结晶形式，其化学式为(I)。一种基本上无杂质的盐酸喹那普利无定形形式，特别是二酮哌嗪化合物，并且符合药典规格，由所述的盐酸喹那普利新颖结晶形式（化学式为I）形成。该结晶形式的盐酸喹那普利是以硝基烷为溶剂的溶剂化物，其中硝基烷是硝基甲烷、硝基乙烷和硝基丙烷。每一种这样的硝基烷溶剂化物都具有特定的特征X-射线衍射图谱。一种制备基本上无杂质，特别是二酮哌嗪化合物，并符合药典规格的盐酸喹那普利无定形形式的过程，使用新颖的结晶盐酸喹那普利作为中间体。该过程包括通过将喹那普利苯甲基酯马来酸盐（化学式为V）的水和有机溶剂混合溶液的pH值调整在7.5-8.5之间，获得自由碱化合物（化学式为V）；在醇溶剂中对该化合物（V）进行催化氢化，在浓盐酸或溶于醇溶剂中的氯化氢的存在下，以及在Pd/C的催化量存在下，获得含有化学式（I）的残留物；通过从硝基烷溶剂中蒸发醇溶剂使所述残留物结晶，得到与硝基烷溶剂的溶剂化物相关的结晶盐酸喹那普利，并在40°C至45°C的温度下，在真空下干燥结晶盐酸喹那普利硝基烷溶剂化物，得到无定形的盐酸喹那普利（化学式为I）。
• Design, Synthesis, and Structure–Activity Relationships of Novel Tetrahydroisoquinolino Benzodiazepine Dimer Antitumor Agents and Their Application in Antibody–Drug Conjugates
  作者：Naidu S. Chowdari、Yong Zhang、Ivar McDonald、Walter Johnson、David R. Langley、Prasanna Sivaprakasam、Robert Mate、Tram Huynh、Srikanth Kotapati、Madhura Deshpande、Chin Pan、Daniel Menezes、Yichong Wang、Chetana Rao、Ganapathy Sarma、Bethanne M. Warrack、Vangipuram S. Rangan、Sung Mei-Chen、Pina Cardarelli、Shrikant Deshpande、David Passmore、Richard Rampulla、Arvind Mathur、Robert Borzilleri、Arvind Rajpal、Gregory Vite、Sanjeev Gangwar

  DOI：10.1021/acs.jmedchem.0c01385

  日期：2020.11.25

  series of tetrahydroisoquinoline-based benzodiazepine dimers were synthesized and tested for in vitro cytotoxicity against a panel of cancer cell lines. Structure–activity relationship investigation of various spacers guided by molecular modeling studies helped to identify compounds with picomolar activity. Payload 17 was conjugated to anti-mesothelin and anti-fucosylated monosialotetrahexosylganglioside

  合成了一系列基于四氢异喹啉的苯并二氮杂二聚体，并测试了其对一组癌细胞系的体外细胞毒性。通过分子建模研究指导的各种间隔基的结构-活性关系研究有助于鉴定具有皮摩尔活性的化合物。有效负载17通过溶酶体可裂解的缬氨酸-瓜氨酸二肽接头，通过异源赖氨酸偶联和细菌转谷氨酰胺酶介导的位点特异性偶联，将其与抗间皮素和抗岩藻糖基化的单唾液酸四己糖基神经节苷脂（FucGM1）抗体偶联。在体外，这些抗体药物偶联物（ADC）对人类癌细胞系表现出显着的细胞毒性和靶标介导的选择性。在小鼠的胃癌和肺癌异种移植模型中，进一步评估了这些ADC的药代动力学和功效。在单剂量ADC- 46（0.02μmol / kg）之后，在这些模型中观察到一致的药代动力学特征，高靶标特异性和强大的抗肿瘤活性。
• [EN] MACROCYCLIC BENZODIAZEPINE DIMERS, CONJUGATES THEREOF, PREPARATION AND USES<br/>[FR] FORMES MACROCYCLIQUES DIMÈRES DES BENZODIAZÉPINES, LEURS CONJUGUÉS, PRÉPARATION ET UTILISATIONS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016209951A1

  公开（公告）日：2016-12-29

  Macrocyclic benzodiazepine dimers having a structure represented by formula (I) where A and B are independently according to formulae (Ia) or (Ib) ]; and the other variables in formulae (I), (Ia), and (Ib) are as defined in the application. Such dimers are useful as anti-cancer agents, especially when used as the drug component in an antibody-drug conjugate (ADC).

  具有由公式（I）表示的结构的大环苯二氮䓬二聚体，其中A和B分别根据公式（Ia）或（Ib）；以及公式（I）、（Ia）和（Ib）中的其他变量如申请中定义。这些二聚体在抗癌药物中非常有用，特别是当作为抗体-药物结合物（ADC）中的药物成分时。
• Studies on angiotensin-converting enzyme inhibitors. I. Syntheses and angiotensinconverting enzyme inhibitory activity of 2-(3-mercaptopropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives.
  作者：KIMIAKI HAYASHI、YASUHIKO OZAKI、KENICHI NUNAMI、TOMOFUMI UCHIDA、JYOJI KATO、KEIZO KINASHI、NAOTO YONEDA

  DOI：10.1248/cpb.31.570

  日期：——

  (3S)-2-[(2S)-3-Mercapto-2-methylpropionyl]-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid [(3S), (2S)-6a] was prepared by the reaction of (3S)-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester [(3S)-2a] or benzyl ester [(3S)-2b] with 3-benzoylthio-2-methylpropionyl chloride (3a), followed by fractional crystallization and removal of the protective group. The absolute configuration of (3S), (2S)-6a was confirmed by X-ray diffraction analysis of the thiazepino [4, 3-b] isoquinoline compound (7) derived from 6a. Resolution of 3-benzoylthio-2-methylpropionic acid (8) was completed by using optically active phenylalanine amide as a resolving agent. The other optical isomers of (3S), (2S)-6a were prepared by the reaction of (3S)- or (3R)-2b with optically active 3a. The in vitro ACE inhibitory activity of each isomer of 6a was evaluated. Among them, (3S), (2S)-6a was found to be the most potent inhibitor with an IC50 value of 8.6×10-9M. Compound (3S), (2S)-6a induced a dose-dependent inhibition of the pressor response to angiotensin I after oral administration to normotensive anesthetized rats. Moreover, (3S), (2S)-6a markedly reduced the systolic blood pressure in renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). The in vivo ACE inhibitory activity and the hypotensive effects of (3S), (2S)-6a were comparable to those of captopril.

  (3S)-2-[(2S)-3-巯基-2-甲基丙酰基]-1, 2, 3, 4-四氢异喹啉-3-羧酸[(3S), (2S)-6a]是通过(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸叔丁基酯[(3S)-2a]或苄基酯[(3S)-2b]与3-苯甲酰硫-2-甲基丙酰氯(3a)反应制备而成，随后通过分馏结晶去除保护基团。通过对由6a衍生的噻唑烯[4, 3-b]异喹啉化合物(7)进行X射线衍射分析，确认了(3S), (2S)-6a的绝对构型。使用光学活性的苯丙氨酸酰胺作为分解剂完成了3-苯甲酰硫-2-甲基丙酸(8)的分解。通过(3S)-或(3R)-2b与光学活性3a反应制备了(3S), (2S)-6a的其他光学异构体。评估了每种6a异构体的体外ACE抑制活性。其中，(3S), (2S)-6a被发现是最有效的抑制剂，IC50值为8.6×10^-9M。化合物(3S), (2S)-6a在该显混合型麻醉大鼠口服给药后，诱导了对血管紧张素I的加压反应的剂量依赖性抑制。此外，(3S), (2S)-6a显著降低了肾性高血压大鼠(RHR)和自发性高血压大鼠(SHR)的收缩压。(3S), (2S)-6a的体内ACE抑制活性和降压效果与卡托普利相当。
• Facile Preparation of optically Pure (3S)- and (3R)- 1, 2, 3, 4-Tetrahydroisoquinoline-3-carboxylic Acid
  作者：KIMIAKI HAYASHI、YASUHIKO OZAKI、KENICHI NUNAMI、NAOTO YONEDA

  DOI：10.1248/cpb.31.312

  日期：——

  Optically pure (3S)-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid (1) was easily obtained by fractional crystallization of its benzyl ester (2b) p-toluenesulfonate, which was prepared from partially racemized 1 hydrochloride, followed by catalytic debenzylation. Similarly, (3R)-1 was prepared by the same procedure. The degree of racemization during the Pictet-Spengler reaction using optically active phenylalanine was determined by 1H-nuclear magnetic resonance (1H-NMR) spectroscopy of the corresponding methyl ester (2a), derived from the reaction product (1), in the presence of a chiral shift reagent.

  光学纯的(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸(1)通过对其苄基酯(2b)的分馏结晶法轻松获得，该苄基酯是由部分消旋的1盐酸盐制备而成，随后经过催化去苄基化。同样，(3R)-1也是通过相同的程序制备的。在使用光学活性的苯丙氨酸进行Pictet-Spengler反应时，通过在存在手性位移试剂的情况下，对反应产物(1)所得到的相应甲基酯(2a)进行1H核磁共振(1H-NMR)光谱分析，确定了消旋化的程度。