(1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol hydrobromide | 1113025-20-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol hydrobromide
• 英文别名: (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentan-1-ol hydrobromide；(1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentan-1-ol;hydrobromide
• CAS: 1113025-20-9
• 化学式: BrH*C₆H₁₃NO₂
• 分子量: 212.087
• InChiKey: SGHBZTGGYMWXHN-YAFCINRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.35
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  66.5
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol hydrobromide 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 异丙醇 、 仲丁醇 为溶剂， 75.0~130.0 ℃ 、600.01 kPa 条件下， 生成 去磺酰胺基MLN4924
  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：

  (1R,4R)-4-(Boc-氨基)-2-环戊烯羧酸 在 吡啶 、 锂硼氢 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 溴 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 异丙醇 为溶剂， -5.0~55.0 ℃ 、250.0 kPa 条件下， 生成 (1S,2S,4R)-4-amino-2-(hydroxymethyl)cyclopentanol hydrobromide
  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

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] INDOLE-SUBSTITUTED PYRROLOPYRIMIDINYL INHIBITORS OF Uba6<br/>[FR] INHIBITEURS DE PYRROLOPYRIMIDINYLE SUBSTITUÉ PAR INDOLE D'UBA6
  申请人：MILLENNIUM PHARM INC

  公开号：WO2014022744A1

  公开（公告）日：2014-02-06

  Disclosed are chemical entities that inhibit Uba6, each of which is a compound of Formula /: Formula (I) or a pharmaceutically acceptable salt thereof, wherein R*1 is -H or -CH3; and Y is Formula (II) or Formula (III), wherein R2 is -H, -CH3 or C1-4 alkyloxycarbonyl; and RS7.1, RS7.2 and RS8.1 are defined herein; pharmaceutical compositions comprising the chemical entities; and methods of using the chemical entities. These chemical entities are useful for treating disorders, particularly cell proliferation disorders, including cancers.

  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，- 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。
• 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。
• INDOLE-SUBSTITUTED PYRROLOPYRIMIDINYL INHIBITORS OF UBA6
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20150210700A1

  公开（公告）日：2015-07-30

  Disclosed are chemical entities that inhibit Uba6, each of which is a compound of Formula /: Formula (I) or a pharmaceutically acceptable salt thereof, wherein R* 1 is —H or —CH 3 ; and Y is Formula (II) or Formula (III), wherein R 2 is —H, —CH 3 or C 1-4 alkyloxycarbonyl; and R S7.1 , R S7.2 and R S8.1 are defined herein; pharmaceutical compositions comprising the chemical entities; and methods of using the chemical entities. These chemical entities are useful for treating disorders, particularly cell proliferation disorders, including cancers.

  本发明涉及抑制Uba6的化学实体，其中每个化合物均为公式/：公式（I）或其药学上可接受的盐，其中R * 1为-H或-CH3; Y为公式（II）或公式（III），其中R2为-H，- 或C1-4烷氧羰基; RS7.1，RS7.2和RS8.1在此被定义; 包括上述化学实体的制药组合物; 以及使用上述化学实体的方法。这些化学实体对于治疗疾病特别是细胞增殖性疾病，包括癌症，非常有用。
• Process for the synthesis of intermediates compounds useful for the preparation of E1 activity activating enzyme inhibitors
  申请人：MILLENNIUM PHARMACEUTICALS, INC.

  公开号：EP2546256A2

  公开（公告）日：2013-01-16

  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)甲基氨基磺酸盐的工艺和合成中间体，它们是 E1 活化酶抑制剂，可用于治疗细胞增殖紊乱，特别是癌症，以及其他与 E1 活性相关的疾病。