3-(4-fluoro-3-nitrophenyl)propionic acid | 160877-40-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-(4-fluoro-3-nitrophenyl)propionic acid
• 英文别名: 4-fluoro-3-nitrophenylpropionic acid；3-(4-fluoro-3-nitrophenyl)propanoic acid
• CAS: 160877-40-7
• 化学式: C₉H₈FNO₄
• 分子量: 213.165
• InChiKey: IHRNYARREWSFGQ-UHFFFAOYSA-N

物化性质

• 熔点：
  97-99 °C
• 沸点：
  395.4±27.0 °C(Predicted)
• 密度：
  1.426±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  3-(4-fluoro-3-nitrophenyl)propionic acid 在 3 A molecular sieve 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 丙酮 为溶剂， 反应 18.5h， 生成 (M)(9S)-2,11-dioxo-4-methoxy-9-methoxycarbonyl-16-nitro-10-azatricyclo[12.2.2.1^3,7]nonadeca-3,5,7(19),14,16,17-hexaene
  参考文献：
  名称：

  Total Synthesis of an Antitumor Agent RA-VII via an Efficient Preparation of Cycloisodityrosine

  摘要：

  Details of efficient syntheses of (9S, 12S)-cycloisodityrosine (6) and a concise total synthesis of RA-VII(1) were described. An intramolecular SNAr-based cycloetherification reaction was employed as the key ring-closure step for construction of the illusive 14-membered m,p-cyclophane. Treatment of methyl N-[N-(tert-butyloxycarbonyl)-L(3-hydroxy-4-methoxyphenylalanyl)]-L-4-fluoro-3-nitrophenylalaninate ((9S,12S)-10) with potassium carbonate in DMSO at room temperature provided a mixture of two atropdiastereomers 20a and 20b in 75% yield that were transformed into cycloisodityrosine 6 in good overall yield. Furthermore, a size-selective ring-forming process was established for methyl N-[N-(tert-butyloxycarbonyl)-L-(3,4-dihydroxyphenlalanyl)]-L-4-fluoro-3- nitrophenylalaninate ((9S,12S)-11). Thus, cyclization of 11 (K2CO3, DMSO, rt), followed by in situ methylation, gave exclusively the 14-membered m,p-cyclphane 20a and 20b without competitive formation of the alternative 15-membered p,p-cyclophane. The selective ring-forming process allowed us to develop one of the shortest and the most efficient synthesis of cycloisodityrosine to date. Computational studies have shown that it was the elimination, but not the addition, step that determined the ring-size selectivity observed in the cyclization of substrate 11. Coupling of 6 with L-N-Boc-Ala (51) proceeded efficiently to provide the corresponding tripeptide 52 that, after removal of the N-Boc function, was allowed to react with another tripeptide 53 to afford the hexapeptide 50 in good overall yield. Saponification followed by liberation of amino function from 50 gave the seco-acid, whose cyclization (DPPA, DMF, NaHCO3) afforded the natural product RA-VII (1).

  DOI：

  10.1021/jo990432w
• 作为产物：
  描述：

  4-氟-3-硝基苄醇 在 盐酸 、 三溴化磷 、 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 0.08h， 生成 3-(4-fluoro-3-nitrophenyl)propionic acid
  参考文献：
  名称：

  SNAr-Based Macrocyclization: An Application to the Synthesis of Vancomycin Family Models

  摘要：

  The first examples of macrocyclization using the intramolecular SNAr reaction are reported. The method has allowed the efficient preparation of the elusive 16-membered macrocyclic COD and DOE rings related to vancomycin. The mild conditions used allow the incorporation of very racemization-prone amino acids, such as p-methoxyphenylglycine, into the peptide chain. After serving as an activator, the nitro group ortho to the diaryl ether linkage is converted either into a chlorine or a hydrogen atom, thus achieving the substitution pattern found in the vancomycin family of glycopeptides. When compound 20 was submitted to the same macrocyclization conditions, two atropisomers 21 and 22 were isolated and characterized.

  DOI：

  10.1021/jo00098a010

文献信息

• Benzylbenzimidazolyl derivatives
  申请人：Stahle Wolfgang

  公开号：US20070066606A1

  公开（公告）日：2007-03-22

  Novel benzyl-benzimidazolyl derivatives as inhibitors of tyrosine kinases, particularly TIE-2, VEGFR, PDGFR, FGFR and/or FLT/KDR, for the treatment of tumors, according to formula (I), wherein the radicals R 1 , R 2 , r and s are defined according to Claim ( 1 ).

  新型苄基-苄并咪唑衍生物作为酪氨酸激酶抑制剂，特别是TIE-2、VEGFR、PDGFR、FGFR和/或FLT/KDR，用于肿瘤治疗，根据式(I)，其中基团R1、R2、r和s的定义如权利要求（1）所述。
• [EN] BENZIMIDAZOL-2-AMINES AS MIDH1 INHIBITORS<br/>[FR] BENZIMIDAZOL-2-AMINES EN TANT QU'INHIBITEURS MIDH1
  申请人：BAYER PHARMA AG

  公开号：WO2015121210A1

  公开（公告）日：2015-08-20

  The present invention relates to benzimidazol-2-amines of general formula (I), in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的苯并咪唑-2-胺化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11和R12如本文所定义，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是肿瘤，作为唯一药剂或与其他活性成分组合使用。
• [DE] BENZYL-BENZIMIDAZOLYLDERIVATE<br/>[EN] BENZYL-BENZIMIDAZOLYL DERIVATIVES<br/>[FR] DERIVES DE BENZYL-BENZIMIDAZOLYLE
  申请人：MERCK PATENT GMBH

  公开号：WO2005028448A1

  公开（公告）日：2005-03-31

  Neue Benzyl-Benzimidazolylderivate als Inhibitoren der Tyrosinkinasen, insbesondere TIE-2, VEGFR, PDGFR, FGFR und/oder FLT/KDR zur Behandlung von Tumoren nach Formel (I) wobei die Reste R1, R2, r und s, nach Anspruch (1) zu definieren sind.

  新的苄基-苯并咪唑衍生物作为酪氨酸激酶抑制剂，特别是TIE-2、VEGFR、PDGFR、FGFR和/或FLT/KDR，用于治疗肿瘤，根据式(I)定义残基R1、R2、r和s，如权利要求书(1)所述。
• A Unified Strategy toward the Synthesis of Acerogenin-Type Macrocycles:  Total Syntheses of Acerogenins A, B, C, and L and Aceroside IV
  作者：Gabriela Islas Gonzalez、Jieping Zhu

  DOI：10.1021/jo981844s

  日期：1999.2.1

  A general strategy for the synthesis of acerogenin-type diarylheptanoids containing an endocyclic biaryl ether bond has been developed, and convergent total syntheses of acerogenin A, B, C, and L and aceroside IV have been accomplished. Cycloetherification of the linear diarylheptanoid 1-(4-fluoro-3-nitrophenyl)-7-(3-hydroxy-4-methoxyphenyl)heptan-3-one (18) under mild conditions (CsF, DMF, 0.01 M

  已经开发了用于合成含有环内联芳基醚键的铜绿蛋白原型二芳基庚烷类化合物的一般策略，并且已经完成了铜绿蛋白原A，B，C和L以及皂苷IV的会聚总合成。线性二芳基庚烷1-（4-氟-3-硝基苯基）-7-（3-羟基-4-甲氧基苯基）庚烷-3-酮（18）在温和条件下（CsF，DMF，0.01 M，rt，5的环醚化） h）得到大环化合物4-甲氧基-17-硝基-2-氧杂三环[13.2.2（3,7）]二十碳-1（18），3,5,7（20），15（19），16-己烯-12一（19），产率95％。除去硝基，然后进行O-去甲基化，得到了金黄色素A（2），还原后得到了金黄色素A（1）。用2,3,4,6-α-D-四苯甲酰基吡喃葡萄糖基溴化物对2进行糖苷化，然后进行皂化，从而得到极好的总收率的皂苷IV（3）。以类似于线性化合物29的关键分子内S（N）Ar反应的方式合成了Acerogenins B（4）和L（5）。提出了环
• [EN] METHOD FOR PREPARING SUBSTITUTED 3-(2-ANILINO-1-CYCLOHEXYL-1H-BENZIMIDAZOL-5-YL)PROPANOIC ACID DERIVATIVES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS D'ACIDE 3-(2-ANILINO-1-CYCLOHEXYL-1H-BENZIMIDAZOL-5-YL)PROPANOÏQUE SUBSTITUÉS
  申请人：BAYER PHARMA AG

  公开号：WO2017017046A1

  公开（公告）日：2017-02-02

  The present invention relates to a method for preparing substituted 3-(2-anilino-1-cyclohexyl-1H-benzimidazol-5-yl)propanoic acid derivatives of the general formula (I) in which R1 represents a hydrogen atom or R1 represents a group selected from the series of C1-C3-alkyl-, C1-C3-alkoxy-, C1-C3-haloalkyl- and C1-C3-haloalkoxy-, R2 represents a hydrogen atom or a C1-C3-alkyl group, R3 represents a hydrogen atom or a C1-C3-alkyl group, R4 represents a cyclohexyl group, which is optionally singly or multiply substituted by a C1-C3-alkyl group, and R5 represents a hydrogen atom or a C1-C6-alkyl group; and also intermediates which may be used to prepare substituted 3-(2-anilino-1- cyclohexyl-1H-benzimidazol-5-yl)propanoic acid derivatives. The present invention also relates to a crystalline form of 3-(2-[4-(trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5- trimethylcyclohexyl]-1H-benzimidazol-5-yl)propanoic acid, pharmaceutical compositions comprising this crystalline form, and also the use of this crystalline form for preparing a medicament for the treatment of a disease.

  本发明涉及一种制备取代的3-(2-苯胺基-1-环己基-1H-苯并咪唑-5-基)丙酸衍生物的方法，其通式为(I)，其中R1表示氢原子或选自C1-C3烷基、C1-C3烷氧基、C1-C3卤代烷基和C1-C3卤代烷氧基的基团，R2表示氢原子或C1-C3烷基，R3表示氢原子或C1-C3烷基，R4表示环己基，可选地单独或多重取代C1-C3烷基，R5表示氢原子或C1-C6烷基；以及可用于制备取代的3-(2-苯胺基-1-环己基-1H-苯并咪唑-5-基)丙酸衍生物的中间体。本发明还涉及3-(2-[4-(三氟甲氧基)苯基]氨基}-1-[(1R,5R)-3,3,5-三甲基环己基]-1H-苯并咪唑-5-基)丙酸的晶体形式、包含该晶体形式的药物组合物，以及使用该晶体形式制备治疗疾病的药物。