4-氯-3-甲氧基苯甲酸 | 85740-98-3

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氯-3-甲氧基苯甲酸
• 中文别名: 3-甲氧基-4-氯基苯甲酸
• 英文名称: 4-chloro-3-methoxybenzoic acid
• 英文别名: 3-methoxy-4-chlorobenzoic acid；4-Chlor-3-methoxy-benzoesaeure
• CAS: 85740-98-3
• 化学式: C₈H₇ClO₃
• mdl: MFCD00269640
• 分子量: 186.595
• InChiKey: OXUUNDMDOOXPKY-UHFFFAOYSA-N

物化性质

• 熔点：
  217.0 to 221.0 °C
• 沸点：
  325.4±22.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  9
• 危险类别码：
  R36/37/38
• 海关编码：
  2918990090
• 安全说明：
  S26,S36/37/39
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H317,H319
• 储存条件：
  室温且干燥

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Chloro-3-methoxybenzoic acid
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
P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician

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Section 3. Composition/information on ingredients.
Ingredient name: 4-Chloro-3-methoxybenzoic acid
CAS number: 85740-98-3

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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: C8H7ClO3
Molecular weight: 186.6

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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, hydrogen chloride.

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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：

  4-氯-3-甲氧基苯甲酸 在 sodium tetrahydroborate 、 正丁基锂 、 氯化亚砜 、 对甲苯磺酰叠氮 、 氢溴酸 、 十六烷基三丁基溴化磷 作用下， 以 水 、 甲苯 、 苯 为溶剂， 反应 48.75h， 生成 4-氯-3-羟基邻氨基苯甲酸
  参考文献：
  名称：

  Synthèse régiosélective de l'acide 4-chloro-3-hydroxyanthranilique, un inhibiteur puissant in vitro de l'enzyme 3-hydroxyanthranilique oxygénase du cerveau de rat

  摘要：

  DOI：

  10.1016/0223-5234(90)90210-t
• 作为产物：
  描述：

  3-甲氧基苯甲酸 在 正丁基锂 、 六氯乙烷 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以39%的产率得到4-氯-3-甲氧基苯甲酸
  参考文献：
  名称：

  通过邻位金属化对取代的甲氧基苯甲酸进行首次常规，直接和区域选择性合成

  摘要：

  在基于邻-金属化位点在芳族化学的新值一般方法邻- ，间- ，和对-茴香酸（1 - 3）（方案1）进行说明。通过改变碱，金属化温度和曝光时间，可以将金属化选择性地定向到任何一个邻位。的金属化邻-茴香酸（1）与小号正丁基锂/ TMEDA在THF中在-78℃下在位置adjacente将羧酸只发生。另一方面，通过n -BuLi / t -BuOK观察到区域选择性的逆转。在LTMP为0°C的情况下，间苯二酸的两个指向矢（2）协同作用以直接将金属引入它们之间，而n - BuLi / t- BuOK优先除去位于甲氧基和羧酸酯（H-4）对位的质子。s- BuLi / TMEDA仅在羧酸酯附近与对茴香酸（3）反应。根据这些方法，已开发出通过多种途径难以达到的，具有多种功能的非常简单的甲氧基苯甲酸的途径（表1）。

  DOI：

  10.1021/jo070082a
• 作为试剂：
  描述：

  4-戊烯-1-醇 、 乙酸烯丙酯 在 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 4-氯-3-甲氧基苯甲酸 、 caesium carbonate 、 (S)-(-)-5,5-二氯-6,6-二甲氧基-2,2-双(二苯基磷酸)-1,1-联苯基 作用下， 以 四氢呋喃 为溶剂， 以81 %的产率得到(S)-octa-1,7-dien-4-ol
  参考文献：
  名称：

  标称和实际 Prorocentin 的全合成

  摘要：

  甲藻衍生的聚醚 prorocentin 是原型丝氨酸/苏氨酸磷酸酶抑制剂冈田酸的共代谢产物。尽管不能错过结构关系并提出了生物合成联系，但目前尚不清楚这些天然产物的生物活性特征是否存在任何相似之处。然而，过去暗示可能需要修改分配给 prorocentin 的结构。事实上，对已发表的光谱的重新检查让人怀疑核心中稠合/螺三环 BCD 环系统的构成。为了澄清这个问题，设计了一个灵活的合成蓝图，使我们能够获得最初提出的结构以及最合理的修正结构。成功的关键是后期金催化的螺环化反应，该反应为异构中心链段提供了出色的选择性。用于制造所需环化前体的催化转化词典包括钛介导的酯亚甲基化/复分解级联，金催化的烯丙基取代的罕见例子，以及通过有机催化不对称醛炔丙基化进行的链延伸。通过 Krische 烯丙基化获得连接到异构核上的翼扇区，然后对所得二不饱和醇进行高选择性钴催化氧化环化，形成 2,5- 用于制造所需环化前

  DOI：

  10.1021/jacs.2c12529

文献信息

• Design, Synthesis, and Antiproliferative Activity of 3,4-Diarylpyrazole-1-carboxamide Derivatives Against Melanoma Cell Line
  作者：Mohammed I. El-Gamal、Hong Seok Choi、Hae-Guk Cho、Jun Hee Hong、Kyung Ho Yoo、Chang-Hyun Oh

  DOI：10.1002/ardp.201000375

  日期：2011.11

  Synthesis of a new series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The biological results indicated that five synthesized compounds (Ig, Ii, IIc, IIg, and IIh) exhibited similar activity to Sorafenib. In addition, three

  描述了一系列新的 3,4-二芳基吡唑-1-甲酰胺衍生物的合成。测试了它们对 A375P 人黑色素瘤细胞系的抗增殖活性，并研究了取代基对二芳基吡唑支架的影响。生物学结果表明，五种合成化合物（Ig、Ii、IIc、IIg 和 IIh）表现出与索拉非尼相似的活性。此外，三种化合物（IIa、IIb 和 IIi）比索拉非尼更有效。在所有这些衍生物中，具有二甲氨基和酚部分的化合物 IIa 对 A375P 人黑色素瘤细胞系显示出最有效的抗增殖活性。通过将最有效的化合物 IIa 对接到 V600E-b-Raf 域中进行虚拟筛选，并研究了结合模式。
• Preparation of (2E,4E)-2-(2-benzyloxyethyl)-5-(3-methoxy-4-chlorophenyl)penta-2,4-dienal as a key intermediate in the synthesis of strobilurin B
  作者：V. A. Popovsky、A. V. Stepanov、N. Ya. Grigorieva

  DOI：10.1007/s11172-012-0215-2

  日期：2012.8

  (2E,4E)-2-(2-Benzyloxyethyl)-5-(4-chloro-3-methoxyphenyl)penta-2,4-dienal was obtained by the condensation of 4-benzyloxybutanal N-tert-butylimine with 4-chloro-3-methoxycinnamic aldehyde with ≥98% configurational purity and 40% yield. When 4-benzyloxy-2-triethylsilylbutanal imine was used, a 7: 3 mixture of the target (2E,4E)-dienal with its (2Z,4E)-isomer was obtained in 60% yield; the latter quantitatively isomerized to the thermodynamically preferable target (2E,4E)-dienal.

  通过4-苄氧基丁醛N-叔丁基亚胺与4-氯-3-甲氧基肉桂醛的缩合反应，获得了构型纯度≥98%、收率40%的(2E,4E)-2-(2-苄氧基乙基)-5-(4-氯-3-甲氧基苯基)戊-2,4-二烯醛。当使用4-苄氧基-2-三乙基硅基丁醛亚胺时，得到了目标(2E,4E)-二烯醛与其(2Z,4E)异构体的7:3混合物，收率为60%；后者定量异构化为热力学上更有利的目标(2E,4E)-二烯醛。
• Design, synthesis, and <i>in vitro</i> antiproliferative and kinase inhibitory effects of pyrimidinylpyrazole derivatives terminating with arylsulfonamido or cyclic sulfamide substituents
  作者：Mahmoud M. Gamal El-Din、Mohammed I. El-Gamal、Mohammed S. Abdel-Maksoud、Kyung Ho Yoo、Daejin Baek、Jungseung Choi、Huiseong Lee、Chang-Hyun Oh

  DOI：10.1080/14756366.2016.1190715

  日期：2016.11.2

  ring at position 3 of the pyrazole nucleus showed the highest mean percentage inhibition value over the whole cancer cell line panel at 10 μM concentration. It showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 1d inhibited the growth of HL-60 (TB), SR leukemia, and T-47D and MCF-7 breast cancer cell line by 135.92%, 119.44%, 95.32%,

  设计，合成和合成了一系列新的取代的嘧啶化合物，它们带有N-苯基吡唑并以芳基和环状磺酰胺基部分终止，在体外作为抗增殖剂针对NCI的53种不同组织的细胞系进行了评估。其中，在吡唑核的3位具有对氯苯磺酰胺基末端部分，乙烯间隔基和4-氯-3-甲氧基苯基环的化合物1d在10μM浓度下在整个癌细胞系中显示出最高的平均抑制百分比值。它在不同癌症类型的许多细胞系中显示了广谱抗增殖活性。例如，化合物1d在10μM下分别抑制HL-60（TB），SR白血病以及T-47D和MCF-7乳腺癌细胞系的生长，分别为135.92％，119.44％，95.32％和82.03％。在相同的测试浓度下，它可以抑制COLO 205结肠，HT29结肠，BT-549乳腺癌和ACHN肾癌细胞系的生长超过80％。但是，在确定化合物1d对最敏感细胞系的IC50时，与HL-60白血病和MRC-5肺成纤维细胞（正常细胞）相比，测试化合物1d对H
• Acetamides and benzamides that are useful in treating sexual dysfunction
  申请人：——

  公开号：US20040029887A1

  公开（公告）日：2004-02-12

  The present invention relates to the use of compounds of formula (I) 1 for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.

  本发明涉及使用式(I)的化合物治疗性功能障碍，以及含有式(I)化合物的组合物用于治疗性功能障碍。
• [EN] SUBSTITUTED BENZAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZAMIDE SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011076678A1

  公开（公告）日：2011-06-30

  The invention relates to compounds of formula I wherein R is hydrogen or lower alkyl; R1 is -(CH2)n-(O)o-heterocycloalkyl or -C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by -(CH2)p-aryl; n is 0, 1 or 2; o is 0 or 1; p is 0, 1 or 2; R2 is CF3, cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl, or is aryl or heteroaryl, wherein the aromatic rings are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF3, OCF3, OCH2CF3, OCH2-cycloalkyl, OCH2C(CH2OH)(CH2C1)(CH3), S-lower alkyl, lower alkoxy, CH2-lower alkoxy, lower alkinyl or cyano, or by-C(O)-phenyl, -O-phenyl, -O- CH2-phenyl, phenyl or -CH2-phenyl, and wherein the phenyl rings may optionally be substituted by halogen, -C(O)-lower alkyl, -C(O)OH or -C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH2-oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; X is a bond, -NR'-, -CH2NH-, -CHR''-, -(CHR'')q-O-, -O-(CHR'')q- or -(CH2)2-; Y is a bond or -CH2- R' is hydrogen or lower alkyl, R'' is hydrogen, lower alkyl, CF3, lower alkoxy, q is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinsons disease, neurodegenerative disorders such as Alzheimers disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  该发明涉及以下式I的化合物，其中R是氢或较低的烷基；R1是-(CH2)n-(O)o-杂环烷基或-C(O)-杂环烷基，其中杂环烷基基团可选择地被较低的烷基，羟基，卤素或-(CH2)p-芳基取代；n为0、1或2；o为0或1；p为0、1或2；R2为CF3，环烷基，可选择地被较低的烷氧基或卤素取代，或为茚-2-基，或为杂环烷基，可选择地被杂芳基取代，或为芳基或杂芳基，其中芳香环可选择地被来自较低的烷基，卤素，杂芳基，羟基，CF3，OCF3，OCH2CF3，OCH2-环烷基，OCH2C(CH2OH)(CH2C1)(CH3)，S-较低的烷基，较低的烷氧基，CH2-较低的烷氧基，较低的炔基或氰基，或-C(O)-苯基，-O-苯基，-O-CH2-苯基，苯基或-CH2-苯基选择的一个或两个取代基取代，其中苯环可选择地被卤素，-C(O)-较低的烷基，-C(O)OH或-C(O)O-较低的烷基取代，或芳香环可选择地被杂环烷基，OCH2-氧杂环戊烷-3-基或O-四氢吡喃-4-基，可选择地被较低的烷基取代；X为键，-NR'-，-CH2NH-，-CHR''-，-(CHR'')q-O-，-O-(CHR'')q-或-(CH2)2-；Y为键或-CH2-；R'为氢或较低的烷基，R''为氢，较低的烷基，CF3，较低的烷氧基，q为0、1、2或3；或其药学上适宜的酸盐。现已发现，该式I的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对于TAAR1。这些化合物可用于治疗抑郁症，焦虑症，躁郁症，注意力缺陷多动障碍（ADHD），与压力有关的疾病，如精神分裂症，帕金森病等神经疾病，阿尔茨海默病等神经退行性疾病，癫痫，偏头痛，高血压，物质滥用和代谢性疾病，如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂异常，能量消耗和吸收异常，体温稳态异常，睡眠和昼夜节律异常，以及心血管疾病。

表征谱图