(1S,2S,4R)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentanol | 1113025-27-6

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: (1S,2S,4R)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentanol
• 英文别名: (1S,2S,4R)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentan-1-ol；(1S,2S,4R)-4-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentan-1-ol
• CAS: 1113025-27-6
• 化学式: C₁₂H₁₄ClN₃O₂
• 分子量: 267.715
• InChiKey: NWIQFXRZYYAXPH-XKSSXDPKSA-N

物化性质

• 沸点：
  499.5±45.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2S,4R)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentanol 在 1,4-diazabicyclo[2.2.2]octan-1-ium chloride 、 N,N-二异丙基乙胺 作用下， 以 乙腈 、 仲丁醇 为溶剂， 5.0~130.0 ℃ 、600.01 kPa 条件下， 生成 氨基磺酸 [(1S,2S,4R)-4-[4-[[(1S)-2,3-二氢-1H-茚-1-基]氨基]-7H-吡咯并[2,3-d]嘧啶-7-基]-2-羟基环戊基]甲基酯
  参考文献：
  名称：

  Process Development and GMP Production of a Potent NAE Inhibitor Pevonedistat

  摘要：

  A practical synthesis of a novel NEDD8-activating enzyme (NAE) inhibitor pevonedistat (MLN4924) is described. Key steps include an enantioselective synthesis of an amino-diol cyclopentane intermediate containing three chiral centers and a novel, regioselective sulfamoylation using N-(tert-butoxycarbonyl)-N-[(triethylenediammonium)sulfonyl]azanide. The linear process, involving six solid isolations, has been carried out in multiple cGMP productions on 15-30 kg scale to produce pevonedistat in 98% (a/a) chemical purity and 25% overall yield.

  DOI：

  10.1021/acs.oprd.5b00209
• 作为产物：
  描述：

  5-烯丙基-4,6-二氯嘧啶 在 sodium periodate 、 四氧化锇 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 异丙醇 为溶剂， 反应 30.57h， 生成 (1S,2S,4R)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentanol
  参考文献：
  名称：

  [EN] INDOLE-SUBSTITUTED PYRROLOPYRIMIDINYL INHIBITORS OF Uba6
  [FR] INHIBITEURS DE PYRROLOPYRIMIDINYLE SUBSTITUÉ PAR INDOLE D'UBA6

  摘要：

  本文披露了抑制Uba6的化学实体，每个实体都是化合物Formula (I)或其药学上可接受的盐，其中R*1为-H或-CH3；Y为Formula (II)或Formula (III)，其中R2为-H，-CH3或C1-4烷氧羰基；RS7.1，RS7.2和RS8.1在此有定义；包括这些化学实体的药物组合物；以及使用这些化学实体的方法。这些化学实体对治疗疾病特别是细胞增殖紊乱，包括癌症，具有用处。

  公开号：

  WO2014022744A1

文献信息

• Process for the synthesis of E1 activating enzyme inhibitors
  申请人：Armitage Ian

  公开号：US20090036678A1

  公开（公告）日：2009-02-05

  The present invention provides processes and synthetic intermediates for the synthesis of 4-substituted ((1S,2S,4R)-2-hydroxy-4-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates, which are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity.

  本发明提供了用于合成4-取代((1S,2S,4R)-2-羟基-4-7H-吡咯并[2,3-d]嘧啶-7-基}环戊基)甲基磺酸酯的过程和合成中间体，该化合物是E1激活酶抑制剂，可用于治疗细胞增殖紊乱，特别是癌症，以及与E1活性相关的其他紊乱。
• [EN] HYDROCHLORIDE SALT OF ((1S,2S,4R)-4-{4-[(1S)-2,3-DIHYDRO-1H-INDEN-1-YLAMINO]-7H-PYRROLO [2,3-D]PYRIMIDIN-7-YL}-2-HYDROXYCYCLOPENTYL)METHYL SULFAMATE<br/>[FR] SEL DE CHLORHYDRATE DE ((1S,2S,4R)-4-{4-[(1S)-2,3-DIHYDRO-1H-INDÈN-1-YLAMINO]-7H-PYRROLO [2,3-D] PYRIMIDIN-7-YLE}-2-HYDROXYCYCLOPENTYLE) MÉTHYLSULFAMATE
  申请人：MILLENNIUM PHARM INC

  公开号：WO2010132110A1

  公开（公告）日：2010-11-18

  Disclosed is a compound of formula (I); crystalline forms thereof, and solvates thereof; pharmaceutical compositions comprising a pharmaceutically effective amount of the compound of formula (I), or a crystalline form thereof, or a solvate thereof, and a pharmaceutically acceptable carrier or diluent; and the use of a compound of formula (I), or a crystalline form thereof, or a solvate thereof, for treating a patient suffering from, or subject to, a pathological condition capable of being ameliorated by inhibiting an El activating enzyme, particularly NAE, including, e.g., cancer.

  本发明公开了一种化合物(I)；其晶体形式和溶剂化物；含有化合物(I)或其晶体形式或溶剂化物的药物组合物，以及药学上有效量的化合物(I)或其晶体形式或溶剂化物和药学上可接受的载体或稀释剂；以及使用化合物(I)或其晶体形式或溶剂化物治疗患有或有可能通过抑制El激活酶（特别是NAE）改善病理状况的患者，包括癌症。
• PROCESS FOR THE SYNTHESIS OF E1 ACTIVATING ENZYME INHIBITORS
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20180079755A1

  公开（公告）日：2018-03-22

  The present invention provides processes and synthetic intermediates for the synthesis of 4-substituted ((4S, 2S, 4R)-2-hydroxy-4-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates, which are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity.

  本发明提供了合成4-取代基((4S, 2S, 4R)-2-羟基-4-7H-吡咯并[2,3-d]嘧啶-7-基}环戊基)甲基磺酸酯的过程和合成中间体，这些化合物是E1激活酶抑制剂，可用于治疗细胞增殖失调疾病，特别是癌症和与E1活性相关的其他疾病。
• HYDROCHLORIDE SALT OF((1S,2S,4R)-4--2-HYDROXYCYCLOPENTYL) METHYL SULFAMATE
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20160030432A1

  公开（公告）日：2016-02-04

  Disclosed is a compound of formula (I): crystalline forms thereof, and solvates thereof; pharmaceutical compositions comprising a pharmaceutically effective amount of the compound of formula (I), or a crystalline form thereof, or a solvate thereof, and a pharmaceutically acceptable carrier or diluent; and the use of a compound of formula (I), or a crystalline form thereof, or a solvate thereof, for treating a patient suffering from, or subject to, a pathological condition capable of being ameliorated by inhibiting an E1 activating enzyme, particularly NAE, including, e.g., cancer.

  本发明涉及一种式(I)的化合物，其晶体形式和溶剂化物；制药有效量的式(I)化合物、其晶体形式或溶剂化物，以及制药可接受的载体或稀释剂构成的制药组合物；以及使用式(I)化合物、其晶体形式或溶剂化物治疗患有或受到能够通过抑制E1激活酶（尤其是NAE）而改善的病理状态的患者，包括癌症等。
• SUBSTITUTED PYRROLO[2,3-D]PYRIMIDINES
  申请人：MILLENNIUM PHARMACEUTICALS, INC.

  公开号：US20160194348A1

  公开（公告）日：2016-07-07

  This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

  本发明涉及抑制E1激活酶的化合物、包含这些化合物的药物组合物以及使用这些化合物的方法。这些化合物对于治疗疾病特别是细胞增殖性疾病，包括癌症、炎症和神经退行性疾病以及与感染和消瘦相关的炎症非常有用。