((1,4-二氮杂双环[2.2.2]辛-1-内盐-1-基)磺酰基)(叔丁氧羰基)酰胺 | 1375958-75-0

• 物质功能分类: 有机原料 - 氨基化合物 - 酰胺类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: ((1,4-二氮杂双环[2.2.2]辛-1-内盐-1-基)磺酰基)(叔丁氧羰基)酰胺
• 英文名称: (1,4-diazabicyclo[2.2.2]octan-1-ium-1-ylsulfonyl)(tert-butoxycarbonyl)amide
• 英文别名: N-(tert-butoxycarbonyl)-N-[(triethylenediammonium)-sulfonyl]azanide；(1,4-Diazabicyclo[2.2.2]octan-1-ium-1-ylsulfonyl)(tert-butoxycarbonyl)amide；N-(4-aza-1-azoniabicyclo[2.2.2]octan-1-ylsulfonyl)-1-[(2-methylpropan-2-yl)oxy]methanimidate
• CAS: 1375958-75-0
• 化学式: C₁₁H₂₁N₃O₄S
• 分子量: 291.371
• InChiKey: KCAURZCKAUWSJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  90.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  去磺酰胺基MLN4924 、 ((1,4-二氮杂双环[2.2.2]辛-1-内盐-1-基)磺酰基)(叔丁氧羰基)酰胺 在 1,4-diazabicyclo[2.2.2]octan-1-ium chloride 、 盐酸 作用下， 以 乙腈 、 水 为溶剂， 以58.5%的产率得到氨基磺酸 [(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：

  三乙烯二胺 、 N-(叔丁氧基羰基)磺酰氯 反应 2.0h， 生成 ((1,4-二氮杂双环[2.2.2]辛-1-内盐-1-基)磺酰基)(叔丁氧羰基)酰胺 、 1,4-diazabicyclo[2.2.2]octan-1-ium chloride
  参考文献：
  名称：

  N-(tert-Butoxycarbonyl)-N-[(triethylenediammonium)sulfonyl]azanide: A Convenient Sulfamoylation Reagent for Alcohols

  摘要：

  A convenient and efficient procedure is described for the sulfamoylation of alcohols using N-(tertbutoxycarbonyl)-N-[(triethylenediammonium)sulfonyl]azanide (1). The ambient temperature stable reagent 1 reacts with phenols as well as primary and secondary alcohols to give high to modest yields. The relative reaction rate of substrates was determined (primary > phenol > secondary tertiary). The reagent's utility as a selective sulfamoylation reagent with polyols is also demonstrated.

  DOI：

  10.1021/ol3009683
• 作为试剂：
  描述：

  ((1,4-二氮杂双环[2.2.2]辛-1-内盐-1-基)磺酰基)(叔丁氧羰基)酰胺 、 去磺酰胺基MLN4924 在 ((1,4-二氮杂双环[2.2.2]辛-1-内盐-1-基)磺酰基)(叔丁氧羰基)酰胺 作用下， 以59的产率得到[(1S,2S)-4-[4-(2,3-Dihydro-1H-inden-1-ylamino)pyrrolo[2,3-D]pyrimidin-7-YL]-2-hydroxycyclopentyl]methyl sulfamate
  参考文献：
  名称：

  Org. Process Res. Dev. 2015, 19, 1299-1307

  摘要：

  DOI：

文献信息

• 肿瘤抑制剂MLN4924的合成方法
  申请人：成都柏睿泰生物科技有限公司

  公开号：CN106854208B

  公开（公告）日：2019-04-09

  本发明公开了肿瘤抑制剂MLN4924的合成方法，属于化学合成领域，该方法以化合物A和化合物E为起始原料，经光延反应、氨化反应、脱保护基和磺酯化四步反应即可合成目标产物MLN4924，具有合成路线短的优点，且原料来源广、成本低、反应条件温和、操作安全，对环境友好、收率高，可达40%以上，适合工业化大规模生产。
• <i>N</i>-(<i>tert</i>-Butoxycarbonyl)-<i>N</i>-[(triethylenediammonium)sulfonyl]azanide: A Convenient Sulfamoylation Reagent for Alcohols
  作者：Ian Armitage、Alexander M. Berne、Eric L. Elliott、Mingkun Fu、Frederick Hicks、Quentin McCubbin、Lei Zhu

  DOI：10.1021/ol3009683

  日期：2012.5.18

  A convenient and efficient procedure is described for the sulfamoylation of alcohols using N-(tertbutoxycarbonyl)-N-[(triethylenediammonium)sulfonyl]azanide (1). The ambient temperature stable reagent 1 reacts with phenols as well as primary and secondary alcohols to give high to modest yields. The relative reaction rate of substrates was determined (primary > phenol > secondary tertiary). The reagent's utility as a selective sulfamoylation reagent with polyols is also demonstrated.
• 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.
• Org. Process Res. Dev. 2015, 19, 1299-1307
  作者：

  DOI：——

  日期：——