5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride | 1426309-48-9

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride
• 英文别名: 5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride；5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridine-3-carboximidamide;hydrochloride
• CAS: 1426309-48-9
• 化学式: C₁₄H₁₁F₂N₅*ClH
• 分子量: 323.733
• InChiKey: SAYWMFNKUAMSSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  80.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 ammonium hydroxide 、 lithium hydroxide monohydrate 、 二碘甲烷 、 potassium carbonate 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 乙腈 、 N,N-dimethyl-d₆-formamide 、 叔丁醇 为溶剂， 反应 80.0h， 生成 methyl 5-(2-amino-2-oxoethyl)-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidine-4-carboxylate
  参考文献：
  名称：

  PYRIMIDINE-BASED TRICYCLIC COMPOUND AND USE THEREOF

  摘要：

  本发明涉及一种嘧啶基三环化合物及其用途，具体而言，涉及一种嘧啶基三环化合物及其在制备治疗相关疾病的药物中的用途。具体而言，公开了一种如式(II)所示的化合物、其立体异构体以及药学上可接受的盐。

  公开号：

  EP4144741A1
• 作为产物：
  描述：

  5-氨基-1-[(2-氟苯基)甲基]-1H-吡唑-3-羧酸乙酯 在 甲烷磺酸 、 sodium methylate 、 formamide 、 lithium chloride 、 三氯氧磷 作用下， 以 环丁砜 、 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 12.0h， 生成 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide hydrochloride
  参考文献：
  名称：

  Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

  摘要：

  The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.

  DOI：

  10.1021/acs.jmedchem.7b00449

文献信息

• BENZYL-SUBSTITUTED PYRAZOLOPYRIDINES AND USE THEREOF
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160002267A1

  公开（公告）日：2016-01-07

  The present application relates to novel benzyl-substituted pyrazolopyridines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

  本申请涉及新颖的苄基取代的吡唑吡啶类化合物，以及它们的制备方法，单独或与其他药物联合治疗和/或预防疾病的用途，以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防心血管疾病的用途。
• Process for preparing substituted 5-fluoro-1H-pyrazolopyridines
  申请人：BAYER INTELLECTUAL PROPERTY GMBH

  公开号：US20130143900A1

  公开（公告）日：2013-06-06

  The present application relates to a novel and efficient process for preparing novel substituted 5-fluoro-1H-pyrazolopyridines of the formula (VI) which are suitable as an intermediate for production of medicaments and for production of medicaments for treatment and/or prophylaxis of cardiovascular disorders. More particularly, the 5-fluoro-1H-pyrazolopyridines of the formula (VI) are suitable for preparation of the compound of the formula (I) which serves for production of medicaments, for production of medicaments for treatment and/or prophylaxis of cardiovascular disorders.

  本申请涉及一种新颖高效的制备新型取代5-氟-1H-吡唑吡啶的方法，其化学式为（VI），该方法适用于作为药物制剂的中间体，用于制备治疗和/或预防心血管疾病的药物。更具体地说，化学式（VI）的5-氟-1H-吡唑吡啶适用于制备化合物的化学式（I），该化合物用于药物制剂的制备，用于制备治疗和/或预防心血管疾病的药物。
• Substituted annellated pyrimidines and use thereof
  申请人：FOLLMANN Markus

  公开号：US20130338137A1

  公开（公告）日：2013-12-19

  The present application relates to novel substituted annellated pyrimidines, methods for production thereof, use thereof alone or in combinations for treating and/or preventing diseases and use thereof for the production of medicinal products for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.

  本申请涉及新型取代的螺合嘧啶类化合物，其生产方法，单独或组合使用用于治疗和/或预防疾病以及用于生产治疗和/或预防疾病的药物产品的用途，特别是用于治疗和/或预防心血管疾病。
• [EN] PROCESS FOR PREPARING METHYL {4,6-DIAMINO-2-[5-FLUORO-1-(2-FLUOROBENZYL)-1H-PYRAZOLO[3,4-B]PYRIDIN-3-YL]PYRIMIDIN-5-YL}CARBAMATE<br/>[FR] PROCÉDÉ DE PRÉPARATION DU {4,6-DIAMINO-2-[5-FLUORO-1-(2-FLUOROBENZYL)-1H-PYRAZOLO[3,4-B]PYRIDIN-3-YL]PYRIMIDIN-5-YL}CARBAMATE DE MÉTHYLE
  申请人：ADVERIO PHARMA GMBH

  公开号：WO2021254981A1

  公开（公告）日：2021-12-23

  The present application relates to a novel and efficient process with high yield for preparing methyl 4,6- diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate of the formula (I) in the crystalline form of modification I, wherein the x-ray diffractogram of the compound of the formula (I) in modification I exhibits peak maxima of the 2 theta angle at 5.9, 6.9, 22.7, in very high purity which is significantly more cost-effective than the process known from the art and can be performed in customary pilot- and production plant-equipment (stirred tank/devices for isolation).

  本申请涉及一种高产率、高效的新型制备甲基4,6-二氨基-2-[5-氟-1-(2-氟苯基)-1H-吡唑[3,4-b]吡啶-3-基]嘧啶-5-基}氨基甲酸甲酯(I式)的结晶形式I的方法，其中式(I)化合物在I型晶体修饰中的X射线衍射图谱在2θ角度处呈现峰值最大值为5.9、6.9、22.7，极其高纯度，比已知工艺更具成本效益，并可在常规中试和生产设备(搅拌槽/分离设备)中进行。
• PROCESS FOR PREPARING SUBSTITUTED 5-FLUORO-1H-PYRAZOLOPYRIDINES
  申请人：ADVERIO PHARMA GMBH

  公开号：US20160009671A1

  公开（公告）日：2016-01-14

  The present application relates to a novel and efficient process for preparing novel substituted 5-fluoro-1H-pyrazolopyridines of the formula (VI) which are suitable as an intermediate for production of medicaments and for production of medicaments for treatment and/or prophylaxis of cardiovascular disorders. More particularly, the 5-fluoro-1H-pyrazolopyridines of the formula (VI) are suitable for preparation of the compound of the formula (I) which serves for production of medicaments, for production of medicaments for treatment and/or prophylaxis of cardiovascular disorders.

  本申请涉及一种新颖高效的制备新型取代的5-氟-1H-吡唑吡啶化合物的方法，该化合物的分子式为(VI)，适用于生产药物的中间体以及用于治疗和/或预防心血管疾病的药物的生产。特别地，分子式为(VI)的5-氟-1H-吡唑吡啶化合物适用于制备分子式为(I)的化合物，该化合物用于生产药物，用于治疗和/或预防心血管疾病。