2-氟-4-甲氧基苯肼盐酸盐 | 940298-93-1

• 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: 2-氟-4-甲氧基苯肼盐酸盐
• 英文名称: (2-fluoro-4-methoxyphenyl)hydrazine hydrochloride
• 英文别名: (2-fluoro-4-methoxyphenyl)hydrazine;hydrochloride
• CAS: 940298-93-1
• 化学式: C₇H₉FN₂O*ClH
• 分子量: 192.621
• InChiKey: IRCLVUNYLCCMEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.54
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  47.3
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2928000090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-氟-4-甲氧基苯肼盐酸盐 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 (6-fluoro-8-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-(5-(trifluoromethyl)-1H-pyrazol-3-yl) - methanone
  参考文献：
  名称：

  Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators

  摘要：

  Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure-activity relationship studies led to the discovery of enantiomerically pure 39 endowed with a good efficacy in rescuing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of gamma-carboline 39 showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.

  DOI：

  10.1021/acs.jmedchem.0c01050
• 作为产物：
  描述：

  2-氟-4-甲氧基苯胺 在 盐酸 、 sodium nitrite 、 tin(ll) chloride 作用下， 以 水 为溶剂， 反应 5.5h， 以56%的产率得到2-氟-4-甲氧基苯肼盐酸盐
  参考文献：
  名称：

  7-氟和6,7-二氟血清素与7-氟和6,7-二氟褪黑激素的合成

  摘要：

  Fischer吲哚合成的Abramovitch适应性降低了7-氟-5-甲氧基色胺的收率，这部分归因于所需脱羧步骤中的分解。因此，通过氨基丁醛（由二乙缩醛原位生成）与2-氟和2,3-二氟-4-甲氧基苯基肼反应，制得7-氟和6,7-二氟-5-甲氧基色胺。转换为相应的5-羟色胺。褪黑素是通过一锅反应制备的，该反应涉及氨基丁醛的原位乙酰化。

  DOI：

  10.1016/j.jfluchem.2006.06.015

文献信息

• Continuous Flow Process For the Synthesis of Phenylhydrazine Salts and Substituted Phenylhydrazine Salts
  申请人：SHANGHAI HYBRID-CHEM TECHNOLOGIES

  公开号：US20190152896A1

  公开（公告）日：2019-05-23

  The present invention provided a continuous flow process for the synthesis of phenylhydrazine salts and substituted phenylhydrazine salts. Diazotization, reduction, acidic hydrolysis and salifying with acids are innovatively integrated together. Using acidic liquids of aniline or substituted aniline, diazotization reagents, reductants and acids as raw materials, phenylhydrazine derivative salts is obtained through the synthesis process, which is a three-step continuous tandem reaction including diazotization, reduction, acidic hydrolysis and salifying. The described synthesis process is a kind of integrated solutions, which is carried out in an integrated reactor. The feed inlets of the integrated reactor are continuously filled with raw materials. In the integrated reactor, diazotization, reduction, acidic hydrolysis and salifying are carried out continuously and orderly, and phenylhydrazine salts or substituted phenylhydrazine salts is obtained in the outlet of the integrated reactor without interruption. The total reaction time is no more than 20 min.

  本发明提供了一种连续流程，用于合成苯肼盐和取代苯肼盐。重氮化、还原、酸性水解和酸化与酸类创新地集成在一起。使用苯胺或取代苯胺的酸性液体、重氮化试剂、还原剂和酸类作为原料，通过合成过程获得苯肼衍生物盐，这是一个包括重氮化、还原、酸性水解和酸化的三步连续串联反应。所述的合成过程是一种集成解决方案，是在一个集成反应器中进行的。集成反应器的进料口连续填充原料。在集成反应器中，重氮化、还原、酸性水解和酸化被连续有序地进行，苯肼盐或取代苯肼盐在集成反应器的出口处获得，没有中断。总反应时间不超过20分钟。
• [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CYSTIC FIBROSIS<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE LA FIBROSE KYSTIQUE
  申请人：FONDAZIONE ST ITALIANO TECNOLOGIA

  公开号：WO2020012427A1

  公开（公告）日：2020-01-16

  The present invention relates to compounds of Formula (Ia) or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof. It further discloses a pharmaceutical composition comprising the compounds of Formula (Ia) and the use of compounds of Formula (Ib), in particular to modulate CFTR protein or ABC protein activities.

  本发明涉及式(Ia)的化合物或其药学上可接受的盐、水合物、溶剂合物、包合物、多形体、立体异构体。进一步披露了一种包含式(Ia)的化合物的药物组合物，以及利用式(Ib)的化合物，特别是用于调节CFTR蛋白或ABC蛋白活性。
• Syntheses of 7-fluoro- and 6,7-difluoroserotonin and 7-fluoro- and 6,7-difluoromelatonin
  作者：Jorge Heredia-Moya、Yoshio Hayakawa、Kenneth L. Kirk

  DOI：10.1016/j.jfluchem.2006.06.015

  日期：2006.9

  The Abramovitch adaption of the Fischer indole synthesis gave low yields of 7-fluoro-5-methoxytryptamine due in part to decomposition during the required decarboxylation step. Therefore, 7-fluoro- and 6,7-difluoro-5-methoxytryptamines were prepared by reaction of aminobutyraldehyde (generated in situ from the diethyl acetal) with 2-fluoro- and 2,3-difluoro-4-methoxyphenylhydrazine, and the products

  Fischer吲哚合成的Abramovitch适应性降低了7-氟-5-甲氧基色胺的收率，这部分归因于所需脱羧步骤中的分解。因此，通过氨基丁醛（由二乙缩醛原位生成）与2-氟和2,3-二氟-4-甲氧基苯基肼反应，制得7-氟和6,7-二氟-5-甲氧基色胺。转换为相应的5-羟色胺。褪黑素是通过一锅反应制备的，该反应涉及氨基丁醛的原位乙酰化。
• Continuous flow process for the synthesis of phenylhydrazine salts and substituted phenylhydrazine salts
  申请人：SHANGHAI HYBRID—CHEM TECHNOLOGIES

  公开号：US11040938B2

  公开（公告）日：2021-06-22

  The present invention provided a continuous flow process for the synthesis of phenylhydrazine salts and substituted phenylhydrazine salts. Diazotization, reduction, acidic hydrolysis and salifying with acids are innovatively integrated together. Using acidic liquids of aniline or substituted aniline, diazotization reagents, reductants and acids as raw materials, phenylhydrazine derivative salts is obtained through the synthesis process, which is a three-step continuous tandem reaction including diazotization, reduction, acidic hydrolysis and salifying. The described synthesis process is a kind of integrated solutions, which is carried out in an integrated reactor. The feed inlets of the integrated reactor are continuously filled with raw materials. In the integrated reactor, diazotization, reduction, acidic hydrolysis and salifying are carried out continuously and orderly, and phenylhydrazine salts or substituted phenylhydrazine salts is obtained in the outlet of the integrated reactor without interruption. The total reaction time is no more than 20 min.

  本发明提供了一种合成苯肼盐和取代苯肼盐的连续流工艺。重氮化、还原、酸性水解和酸盐化被创新性地整合在一起。以苯胺或取代苯胺的酸性液体、重氮化试剂、还原剂和酸为原料，通过重氮化、还原、酸性水解和盐化三步连续串联反应的合成工艺，获得苯肼衍生物盐。所述合成工艺是一种一体化解决方案，在一体化反应器中进行。集成反应器的进料口连续注入原料。在一体化反应器中，重氮化、还原、酸性水解和盐化连续有序地进行，在一体化反应器的出口处不间断地得到苯肼盐或取代苯肼盐。总反应时间不超过 20 分钟。
• COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CYSTIC FIBROSIS
  申请人：Fondazione Istituto Italiano di Tecnologia

  公开号：EP3820867A1

  公开（公告）日：2021-05-19