tert-butyl (1S,2R,4S,5R)-7-oxo-3-oxa-6-azatricyclo[3.2.1.0^2,4]octan-6-carboxylate | 244057-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl (1S,2R,4S,5R)-7-oxo-3-oxa-6-azatricyclo[3.2.1.0^2,4]octan-6-carboxylate
• 英文别名: tert-butyl (1S,2R,4S,5R)-7-oxo-3-oxa-6-azatricyclo[3.2.1.02,4]octane-6-carboxylate；tert-butyl (4S,5R,6R,7S)-8-oxo-14-oxa-11-azatricyclooctane-11-carboxylate；racemic-(1S,2R,4S,5R)-tert-butyl 7-oxo-3-oxa-6-azatricyclo[3.2.1.02,4]octane-6-carboxylate
• CAS: 244057-70-3
• 化学式: C₁₁H₁₅NO₄
• 分子量: 225.244
• InChiKey: CKSVPIZNXAIFIN-OSMVPFSASA-N

物化性质

• 熔点：
  120-122 °C
• 沸点：
  377.5±35.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (1S,2R,4S,5R)-7-oxo-3-oxa-6-azatricyclo[3.2.1.0^2,4]octan-6-carboxylate 在 sodium tetrahydroborate 、 水 、 红铝 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 (+)-(1S,2R,4R)-4-氨基-2-(羟甲基)-1-环戊醇
  参考文献：
  名称：

  2-Azabicyclo [2.2.1] hept-5-en-3-one epoxy：通用的中间体，用于合成环戊基碳环2-脱氧，3-脱氧和阿拉伯核糖核苷类似物

  摘要：

  5，6-环氧-外-2--2-氮杂双环[2.2.1]庚-3-已被用作合成2-脱氧，3-脱氧和芳基-环戊基碳环核苷的通用中间体。报道了（+）碳环胸苷13的有效的，短的合成。

  DOI：

  10.1016/s0040-4039(99)01113-2
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 120.0h， 生成 tert-butyl (1S,2R,4S,5R)-7-oxo-3-oxa-6-azatricyclo[3.2.1.0^2,4]octan-6-carboxylate
  参考文献：
  名称：

  [EN] COMPOUNDS TARGETING PRMT5
  [FR] COMPOSÉS CIBLANT PRMT5

  摘要：

  本文提供了式（I）的化合物或其药用盐，包括含有本文描述的化合物（包括本文描述的化合物的药用盐）的药物组合物以及合成这些化合物的方法。本文还提供了使用式（I）的化合物或其药用盐治疗疾病和/或症状的方法。

  公开号：

  WO2020205867A1

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO NTRK<br/>[FR] COMPOSÉS ET COMPOSITIONS UTILES POUR TRAITER DES TROUBLES ASSOCIÉS AU GÈNE NTRK
  申请人：BLUEPRINT MEDICINES CORP

  公开号：WO2017035354A1

  公开（公告）日：2017-03-02

  This invention relates to inhibitors of NTRK that are active against wild-type NTRK and its resistant mutants.

  这项发明涉及对NTRK的抑制剂，对野生型NTRK及其耐药突变体具有活性。
• Highly selective directed hydrogenation of enantiopure 4-( tert -butoxycarbonylamino)cyclopent-1-enecarboxylic acid methyl esters
  作者：Mark E.B Smith、Nadine Derrien、Michael C Lloyd、Stephen J.C Taylor、David A Chaplin、Raymond McCague

  DOI：10.1016/s0040-4039(00)02210-3

  日期：2001.2

  The use of both N-tert-butoxycarbonylamino- and hydroxyl-directed hydrogenation methodology to yield essentially single diastereomers of 3-(tert-butoxycarbonylamino)-4-hydroxycyclopentanecarboxylic acid methyl esters and 3-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid methyl esters is described. These results incorporate the first reported carbamate-directed hydrogenations of functionalised

  同时使用的ñ -叔叔丁氧羰和羟基定向加氢方法得到的3-基本上单非对映体（叔丁氧基羰基）-4- hydroxycyclopentanecarboxylic酸甲酯和3-（叔丁氧基羰基）环戊烷羧酸甲酯进行说明。这些结果结合了第一个报道的官能化环戊烯的氨基甲酸酯定向加氢反应。
• Compounds and compositions useful for treating disorders related to NTRK
  申请人：BLUEPRINT MEDICINES CORPORATION

  公开号：US10017512B2

  公开（公告）日：2018-07-10

  This disclosure relates to inhibitors of NTRK that are active against wild-type NTRK and its resistant mutants, such as compounds of Formula (I):

  本公开涉及对野生型 NTRK 及其抗性突变体有活性的 NTRK 抑制剂，如式 (I) 化合物：
• Compounds targeting PRMT5
  申请人：ALIGOS THERAPEUTICS, INC.

  公开号：US11198699B2

  公开（公告）日：2021-12-14

  Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

  本文提供了式(I)化合物或其药学上可接受的盐、包括本文所述化合物的药物组合物（包括本文所述化合物的药学上可接受的盐）以及合成这些化合物的方法。本文还提供了用式（I）化合物或其药学上可接受的盐治疗疾病和/或病症的方法。
• Base Pairing and Replicative Processing of the Formamidopyrimidine-dG DNA Lesion
  作者：Matthias Ober、Heiko Müller、Carsten Pieck、Johannes Gierlich、Thomas Carell

  DOI：10.1021/ja0549188

  日期：2005.12.1

  The 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG) is one of the major DNA lesions found after oxidative stress in cells. To clarify the base pairing and coding potential of this major DNA lesion with the aim to estimate its mutagenic effect, we prepared oligonucleotides containing a cyclopentane based analogue of the DNA lesion (cFaPydG). In addition, oligonucleoticles containing the cyclopentane analogue of 2'-deoxyguanosine (cdG), and oligonucleotides containing 8-oxo-7,8-dihydro2'-deoxyguanosine (8-oxodG) were synthesized. The thermodynamic stability of duplexes containing these building blocks and all canonical counterbases were determined by concentration dependent melting-point measurements (van't Hoff plots). The data reveal that cFaPydG greatly destabilizes a DNA duplex (Delta Delta G(o)298K approximate to 2-4 kcal mol(-1)). The optimal base pairing partner for the cFaPydG lesion is dC. Investigation of duplexes containing dG and cdG shows that the effect of substituting the deoxyribose by a cyclopentane moiety is marginal. The data also provide strong evidence that the FaPydG lesion is unable to form a base pair with dA. Our computational studies indicate that the syn-conformation required for base pairing with dA is energetically unfavorable. This is in contrast to 8-oxodG for which the syn-conformation represents the energetic minimum. Kinetic primer extension studies using S. cerevisiae Pol eta reveal that cFaPydG is replicated in an error-free fashion. dC is inserted 2-3 orders of magnitude more efficiently than dT or CIA, showing that FaPydG is a lesion which retains the coding potential of dG. This is also in contrast to 8-oxodG, for which base pairing with dC and dA was established.