6-溴-1-甲基-1H-吲唑-5-醇 | 1403767-19-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 6-溴-1-甲基-1H-吲唑-5-醇
• 英文名称: 6-bromo-1-methyl-1H-indazol-5-ol
• 英文别名: 6-bromo-1-methylindazol-5-ol
• CAS: 1403767-19-0
• 化学式: C₈H₇BrN₂O
• 分子量: 227.06
• InChiKey: HQZWXUJQORXMPL-UHFFFAOYSA-N

物化性质

• 沸点：
  325.5±22.0 °C(Predicted)
• 密度：
  1.76±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  38
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-溴-1-甲基-1H-吲唑-5-醇 在 potassium phosphate monohydrate 、 dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) 、 二碳酸二叔丁酯 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 1-羟基苯并三唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~65.0 ℃ 、344.75 kPa 条件下， 反应 113.0h， 生成 N-[3-氟-4-[[1-甲基-6-(1H-吡唑-4-基)-1H-吲唑-5-基]氧基]苯基]-1-(4-氟苯基)-1,2-二氢-6-甲基-2-氧代-3-吡啶甲酰胺
  参考文献：
  名称：

  Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an N1-Methylindazole

  摘要：

  The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important N1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.

  DOI：

  10.1021/op400317z
• 作为产物：
  描述：

  2-甲基-4-甲氧基苯胺 在 盐酸 、 aluminum (III) chloride 、 potassium tert-butylate 、 溴 、 溶剂黄146 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 22.0h， 生成 6-溴-1-甲基-1H-吲唑-5-醇
  参考文献：
  名称：

  Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an N1-Methylindazole

  摘要：

  The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important N1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.

  DOI：

  10.1021/op400317z

文献信息

• [EN] PYRIMIDINE DERIVATIVES AS PGE2 RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QUE MODULATEURS DES RÉCEPTEURS DES PGE2
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：WO2018210988A1

  公开（公告）日：2018-11-22

  The present invention relates to pyrimidine derivatives of formula (I) wherein (R1)n, R3, R4a, R4b, R5a, R5b and Ar1 are as described in the description and their use in the treatment of cancer by modulating an immune response comprising a reactivation of the immune system in the tumor. The invention further relates to novel benzofurane and benzothiophene derivatives of formula (II) and their use as pharmaceuticals, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as modulators of the prostaglandin 2 receptors EP2 and/or EP4.

  本发明涉及式(I)的嘧啶衍生物，其中(R1)n，R3，R4a，R4b，R5a，R5b和Ar1如描述中所述，以及它们通过调节免疫反应，包括肿瘤中免疫系统的再激活，用于治疗癌症。本发明进一步涉及新颖的苯并呋喃和苯并噻吩衍生物式(II)，及其作为药物的使用，其制备，药用可接受的盐，及其作为药物的使用，以及包含式(I)中一个或多个化合物的药物组合物，尤其是它们作为前列腺素2受体EP2和/或EP4的调节剂的使用。
• An Alternative Indazole Synthesis for Merestinib
  作者：Yu Lu、Kevin P. Cole、Jared W. Fennell、Todd D. Maloney、David Mitchell、Ramesh Subbiah、Balakumar Ramadas

  DOI：10.1021/acs.oprd.8b00016

  日期：2018.3.16

  A new synthesis of a key indazole-containing building block for the MET kinase inhibitor merestinib was designed and demonstrated. Crucial to the successful construction of the challenging indazole is an SNAr reaction, which forges the heterocyclic ring. Continuous processing was applied to two of the five steps: nitration of a benzaldehyde and high-temperature hydrolysis of an aniline to phenol. Compared

  设计并证明了MET激酶抑制剂merestinib的关键化合物的新合成。成功构建具有挑战性的吲唑的关键是S N Ar反应，该反应可锻造杂环。对五个步骤中的两个步骤进行了连续处理：苯甲醛的硝化和苯胺的高温水解为苯酚。与高度发展的历史路线相比，新路线在产品质量以及潜在的可制造性和鲁棒性方面显示出明显的优势。
• COMPOUND HAVING AXL AND C-MET KINASE INHIBITORY ACTIVITY, PREPARATION THEREOF AND APPLICATION THEREOF
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：EP4029862A1

  公开（公告）日：2022-07-20

  A compound having Axl and c-Met kinase inhibitory activity, a preparation method therefor and an application thereof. Specifically, a compound having the structure represented by formula (I), a preparation method therefor and an application thereof in the preparation of a medication for the treatment and/or prevention of tumor-associated diseases and/or kinase-related diseases.

  具有Axl和c-Met激酶抑制活性的化合物，其制备方法及其应用。具体来说，该化合物具有由式（I）表示的结构，其制备方法及其在制备用于治疗和/或预防与肿瘤相关的疾病和/或激酶相关疾病的药物中的应用。
• TRICYCLIC FURAN-SUBSTITUTED PIPERIDINEDIONE COMPOUND
  申请人：Medshine Discovery Inc.

  公开号：EP3848371A1

  公开（公告）日：2021-07-14

  Disclosed are a series of tricyclic furan-substituted piperidinedione compounds and an application thereof in preparing a drug for treating a disease related to CRBN protein. In particular, disclosed is a derivative compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

  公开了一系列三环呋喃取代的哌啶二酮化合物及其在制备治疗与 CRBN 蛋白质有关的疾病的药物中的应用。特别是公开了由式（I）代表的衍生物化合物或其药学上可接受的盐。
• [EN] COMPOUND HAVING AXL AND C-MET KINASE INHIBITORY ACTIVITY, PREPARATION THEREOF AND APPLICATION THEREOF<br/>[FR] COMPOSÉ AYANT UNE ACTIVITÉ INHIBITRICE DE LA KINASE AXL ET DE LA KINASE C-MET, SA PRÉPARATION ET SON APPLICATION<br/>[ZH] 具有Axl与c-Met激酶抑制活性的化合物及其制备和应用
  申请人：SHANGHAI INST MATERIA MEDICA CAS

  公开号：WO2021043217A1

  公开（公告）日：2021-03-11

  一种具有Axl与c-Met激酶抑制活性的化合物及其制备方法和应用。具体地，具有式(I)所示结构的化合物、其制备方法及其在制备治疗和/或预防肿瘤相关疾病和/或激酶相关疾病的药物中的应用。