methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldiphenylsilyl)oxy)propanoate | 870820-64-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldiphenylsilyl)oxy)propanoate
• 英文别名: Methyl 3-[tert-butyl(diphenyl)silyl]oxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 870820-64-7
• 化学式: C₂₅H₃₅NO₅Si
• 分子量: 457.642
• InChiKey: UIULHMFQHIKXAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldiphenylsilyl)oxy)propanoate 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 生成 2-(tert-butoxycarbonylamino)-3-(tert-butyldiphenylsiloxy)propanal
  参考文献：
  名称：

  氢化锡介导的仲酰胺自由基环化导致取代的吡咯烷酮。第2部分。在合成芳族海藻酸类似物中的应用

  摘要：

  据报道，从D-丝氨酸开始对映体选择性合成苯基别嘌呤类化合物。关键步骤使用锡介导的仲酰胺环化以优异的产率（约80％）生产三取代的吡咯烷酮。全反式非对映异构体的主要形成与可逆环化相一致，以提供热力学上更稳定的产物。

  DOI：

  10.1039/a905809e
• 作为产物：
  描述：

  Boc-L-丝氨酸甲酯 、 叔丁基二苯基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldiphenylsilyl)oxy)propanoate
  参考文献：
  名称：

  Synthesis and Conformational Analysis of a Non-Amidine Factor Xa Inhibitor That Incorporates 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 Binding Element

  摘要：

  Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.

  DOI：

  10.1021/jm049884d

文献信息

• 三并环类化合物，包含其的药物组合物及其用途
  申请人：四川科伦博泰生物医药股份有限公司

  公开号：CN115028649A

  公开（公告）日：2022-09-09

  本发明属于药物化学领域，涉及三并环类化合物，包含其的药物组合物及其用途。具体地，本发明涉及一种具有式I结构的化合物，其表现出较好的SHP2抑制活性，可以作为高效的SHP2抑制剂，用于预防和/或治疗SHP2相关疾病。
• Synthesis and Conformational Analysis of a Non-Amidine Factor Xa Inhibitor That Incorporates 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-<i>c</i>]pyridine as S4 Binding Element
  作者：Noriyasu Haginoya、Syozo Kobayashi、Satoshi Komoriya、Toshiharu Yoshino、Makoto Suzuki、Takashi Shimada、Kengo Watanabe、Yumiko Hirokawa、Taketoshi Furugori、Takayasu Nagahara

  DOI：10.1021/jm049884d

  日期：2004.10.1

  Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.
• Efficient tin hydride-mediated radical cyclisation of secondary amides leading to substituted pyrrolidinones. Part 2. Application to the synthesis of aromatic kainic acid analogues
  作者：Justin S. Bryans、Jonathan M. Large、Andrew F. Parsons

  DOI：10.1039/a905809e

  日期：——

  An enantioselective synthesis of phenyl allokainoid, starting from D-serine, is reported. Tin-mediated cyclisation of a secondary amide was used in the key step to produce a trisubstituted pyrrolidinone in excellent yield (ca. 80%). The predominant formation of the all-trans diastereoisomer is consistent with a reversible cyclisation to give the thermodynamically more stable product.

  据报道，从D-丝氨酸开始对映体选择性合成苯基别嘌呤类化合物。关键步骤使用锡介导的仲酰胺环化以优异的产率（约80％）生产三取代的吡咯烷酮。全反式非对映异构体的主要形成与可逆环化相一致，以提供热力学上更稳定的产物。