6-溴-1,3-二氯异喹啉 | 552331-05-2

• 物质功能分类: 医药中间体 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 6-溴-1,3-二氯异喹啉
• 英文名称: 6-bromo-1,3-dichloroisoquinoline
• CAS: 552331-05-2
• 化学式: C₉H₄BrCl₂N
• 分子量: 276.947
• InChiKey: YRSSIZNHQQNESH-UHFFFAOYSA-N

物化性质

• 熔点：
  124-128 °C
• 沸点：
  383.4±37.0 °C(Predicted)
• 密度：
  1.765±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险品标志：
  T
• 安全说明：
  S26,S39,S45
• 危险类别码：
  R25,R41,R37/38
• WGK Germany：
  3
• 海关编码：
  2933499090
• 危险品运输编号：
  UN 2811
• 包装等级：
  III
• 危险类别：
  8,6.1
• 危险性防范说明：
  P261,P280,P301+P310,P305+P351+P338
• 危险性描述：
  H301,H315,H318,H335,H413

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 6-Bromo-1,3-dichloroisoquinoline
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H301: Toxic if swallowed
H315: Causes skin irritation
H318: Causes serious eye damage
H335: May cause respiratory irritation
May cause long lasting harmful effects to aquatic life
H413:
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

---

Section 3. Composition/information on ingredients.
Ingredient name: 6-Bromo-1,3-dichloroisoquinoline
CAS number: 552331-05-2

---

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
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C9H4BrCl2N
Molecular weight: 276.9

---

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, hydrogen chloride, hydrogen bromide.

---

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
UN Number: UN2811 Class: 6.1 Packing group: III
Proper shipping name: TOXIC SOLIDS, ORGANIC, N.O.S. (6-Bromo-1,3-dichloroisoquinoline)

---

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

反应信息

• 作为反应物：
  描述：

  6-溴-1,3-二氯异喹啉 在 HI 作用下， 以 溶剂黄146 、 乙酸乙酯 为溶剂， 以50%的产率得到6-溴-3-氯异喹啉
  参考文献：
  名称：

  Kinase inhibitors

  摘要：

  具有以下化学式的化合物对抑制蛋白激酶很有用。还公开了抑制蛋白激酶的组合物以及在患者中抑制蛋白激酶的方法。

  公开号：

  US20030187026A1
• 作为产物：
  描述：

  6-溴异喹啉-1,3-二醇 在 苯膦酰二氯 作用下， 反应 3.0h， 以43.4%的产率得到6-溴-1,3-二氯异喹啉
  参考文献：
  名称：

  一种药物中间体双取代含氮杂环的胺类化合 物的合成

  摘要：

  一种药物中间体双取代含氮杂环的胺类化合物的合成，是以5‑溴‑2‑羧基苯乙酸、尿素、邻二氯苯作为原料进行反应，得到6‑溴异喹啉‑1，3(2H，4H)‑二酮；6‑溴异喹啉‑1，3(2H，4H)‑二酮与苯基磷酰二氯反应，添加四氢呋喃析出，调节pH值后过柱，得到1，3‑二氯‑6‑溴异喹啉；再加冰乙酸、赤磷、氢碘酸，反应后TLC确定反应完全，滤液和滤饼反复精细处理，得到3‑氯‑6‑溴异喹啉；将五水硫酸铜、6‑溴‑3‑氯异喹啉、大量15％的氨水在高压釜中反应，提取并多次按照不同要求过柱，得到最终产物3‑氯‑6‑氨基异喹啉。

  公开号：

  CN108929270B

文献信息

• Palladium(I) Dimer Enabled Extremely Rapid and Chemoselective Alkylation of Aryl Bromides over Triflates and Chlorides in Air
  作者：Indrek Kalvet、Theresa Sperger、Thomas Scattolin、Guillaume Magnin、Franziska Schoenebeck

  DOI：10.1002/anie.201701691

  日期：2017.6.12

  Disclosed herein is the first general chemo- and site-selective alkylation of C-Br bonds in the presence of COTf, C-Cl and other potentially reactive functional groups, using the air-, moisture-, and thermally stable dinuclear PdI catalyst, [Pd(μ-I)PtBu3 ]2 . The bromo-selectivity is independent of the substrate and the relative positioning of the competing reaction sites, and as such fully predictable

  本文公开的是在 COTf、C-Cl 和其他潜在反应性官能团存在下，使用空气稳定、水分稳定和热稳定的双核 PdI 催化剂，对 C-Br 键进行第一个常规化学和位点选择性烷基化，[ Pd(μ-I)PtBu3]2 。溴选择性与底物和竞争反应位点的相对位置无关，因此完全可预测。在室温和开瓶反应条件下以极高的速度（<5 分钟反应时间）引入伯烷基链和仲烷基链。
• PYRAZOLOPYRIDINE PYRAZOLOPYRIMIDINE AND RELATED COMPOUNDS
  申请人：Global Blood Therapeutics, Inc.

  公开号：US20150315198A1

  公开（公告）日：2015-11-05

  In one aspect this invention relates generally to compounds of Formula: and sub-formulas thereof, or a tautomer of each thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, where X 1 , L 1 , L 3 , and R 3 are described herein.

  在一个方面，这项发明通常涉及以下式的化合物： 及其亚式，或每个亚式的重排异构体，每个的药学上可接受的盐，或每个前述的药学上可接受的溶剂，其中X 1 ，L 1 ，L 3 和R 3 如本文所述。
• Rapid Room‐Temperature, Chemoselective C−C Coupling of Poly(pseudo)halogenated Arenes Enabled by Palladium(I) Catalysis in Air
  作者：Indrek Kalvet、Guillaume Magnin、Franziska Schoenebeck

  DOI：10.1002/anie.201609635

  日期：2017.2

  we herein report a general method based on PdI that allows for an a priori predictable chemoselective Csp2 -Csp2 coupling at C-Br in preference to C-OTf and C-Cl bonds, regardless of the electronic or steric bias of the substrate. The C-C bond formations are extremely rapid (<5 min at RT) and are catalyzed by an air- and moisture-stable PdI dimer under open-flask conditions.

  尽管Pd0催化的偶联反应中的化学选择性通常是不直观的，并且是配体/催化剂，底物和反应条件之间复杂相互作用的结果，但我们在此报告了一种基于PdI的通用方法，该方法可实现事先可预测的化学选择性Csp2- Csp2在C-Br处的偶联优先于C-OTf和C-Cl键，而与底物的电子或空间偏压无关。CC键的形成非常快（在RT下<5分钟），并在开瓶条件下被空气和水分稳定的PdI二聚体催化。
• Bicyclic Sulfonamide Compounds as Sodium Channel Inhibitors
  申请人：AMGEN INC.

  公开号：US20160137636A1

  公开（公告）日：2016-05-19

  The present invention provides compounds of Formula I or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了I式化合物或其药学上可接受的盐，其为电压门控钠通道抑制剂，特别是Nav1.7。该化合物可用于治疗可通过钠通道抑制治疗的疾病，如疼痛障碍。还提供了含有本发明化合物的制药组合物。
• Sulfonamides as Selective Na_V1.7 Inhibitors: Optimizing Potency and Pharmacokinetics While Mitigating Metabolic Liabilities
  作者：Matthew M. Weiss、Thomas A. Dineen、Isaac E. Marx、Steven Altmann、Alessandro Boezio、Howard Bregman、Margaret Chu-Moyer、Erin F. DiMauro、Elma Feric Bojic、Robert S. Foti、Hua Gao、Russell Graceffa、Hakan Gunaydin、Angel Guzman-Perez、Hongbing Huang、Liyue Huang、Michael Jarosh、Thomas Kornecook、Charles R. Kreiman、Joseph Ligutti、Daniel S. La、Min-Hwa Jasmine Lin、Dong Liu、Bryan D. Moyer、Hanh N. Nguyen、Emily A. Peterson、Paul E. Rose、Kristin Taborn、Beth D. Youngblood、Violeta Yu、Robert T. Fremeau

  DOI：10.1021/acs.jmedchem.6b01851

  日期：2017.7.27

  Several reports have recently emerged regarding the identification of heteroarylsulfonamides as Na(V)1.7 inhibitors that demonstrate high levels of selectivity over other Na-V isoforms. The optimization of a series of internal Na(V)1.7 leads that address a number of metabolic liabilities including bioactivation, PXR activation, as well as CYP3A4 induction and inhibition led to the identification of potent and selective inhibitors that demonstrated favorable pharmacokinetic profiles and were devoid of the aforementioned liabilities. The key to achieving this within a series prone to transporter-mediated clearance was the identification of a small range of optimal cLogD values and the discovery of subtle PXR SAR that was not lipophilicity dependent. This enabled the identification of compound 20, which was advanced into a target engagement pharmacodynamic model where it exhibited robust reversal of histamine-induced scratching bouts in mice.