methyl (1S,4R)-4-(tritylamino)cyclopent-2-ene-1-carboxylate | 1113025-16-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: methyl (1S,4R)-4-(tritylamino)cyclopent-2-ene-1-carboxylate
• 英文别名: Methyl (1S,4R)-4-(tritylamino)cyclopent-2-ene-1-carboxylate
• CAS: 1113025-16-3
• 化学式: C₂₆H₂₅NO₂
• 分子量: 383.49
• InChiKey: IHYJPPPYWCLXET-YKSBVNFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (1S,4R)-4-(tritylamino)cyclopent-2-ene-1-carboxylate 在 叔丁基过氧化氢 、 硼烷四氢呋喃络合物 、 L-(+)-酒石酸二乙酯 、 palladium on activated charcoal 、 氢气 、 二异丁基氢化铝 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 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：

  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：

  (-)-文斯内酯 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 生成 methyl (1S,4R)-4-(tritylamino)cyclopent-2-ene-1-carboxylate
  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。
• PROCESS FOR THE SYNTHESIS OF E1 ACTIVATING ENZYME INHIBITORS
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20150080573A1

  公开（公告）日：2015-03-19

  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)甲基磺酸盐的过程和合成中间体，这些化合物是E1激活酶抑制剂，对于治疗细胞增殖障碍特别是癌症以及与E1活性相关的其他疾病非常有用。
• 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，-CH3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。
• US9593121B2
  申请人：——

  公开号：US9593121B2

  公开（公告）日：2017-03-14
• Process Development and GMP Production of a Potent NAE Inhibitor Pevonedistat
  作者：Ian Armitage、Eric L. Elliott、Frederick Hicks、Marianne Langston、Ashley McCarron、Quentin J. McCubbin、Erin O’Brien、Matt Stirling、Lei Zhu

  DOI：10.1021/acs.oprd.5b00209

  日期：2015.9.18

  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.