N-Boc-3-methyl-5-piperidone | 1509382-47-1

• 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: N-Boc-3-methyl-5-piperidone
• 英文别名: 1-Boc-5-methyl-3-piperidinone；tert-butyl 3-methyl-5-oxopiperidine-1-carboxylate
• CAS: 1509382-47-1
• 化学式: C₁₁H₁₉NO₃
• 分子量: 213.277
• InChiKey: PIXOEWQIZRMJQU-UHFFFAOYSA-N

物化性质

• 沸点：
  298.8±33.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-Boc-3-methyl-5-piperidone 在 盐酸 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction

  摘要：

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.055
• 作为产物：
  描述：

  (3R,5R)-1-benzyl-5-methylpiperidin-3-ol 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 戴斯-马丁氧化剂 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 N-Boc-3-methyl-5-piperidone
  参考文献：
  名称：

  Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction

  摘要：

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.055

文献信息

• [EN] HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS<br/>[FR] COMPOSÉS SPIRO HÉTÉROCYCLIQUES CONSTITUANT DES INHIBITEURS DU RÉCEPTEUR DE L'AM2
  申请人：UNIV SHEFFIELD

  公开号：WO2020099882A1

  公开（公告）日：2020-05-22

  Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein HET, R1, R2, R3, R4, R5, L, L1, X1, X2, X3 and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.

  揭示了式(I)的化合物及其药学上可接受的盐：其中HET、R1、R2、R3、R4、R5、L、L1、X1、X2、X3和q如本文所定义。这些化合物是肾上腺髓质素受体亚型2（AM2）的抑制剂。还揭示了这些化合物用于治疗调节AM2的疾病，包括增殖性疾病如癌症；包含这些化合物的药物组合物；制备这些化合物的方法；以及制备这些化合物的有用中间体。
• 一种4-Boc-2,5,6,7-四氢吡唑并[4,3-b]吡啶及其衍生物的制备方法
  申请人：海南梵圣生物科技有限公司

  公开号：CN111978321A

  公开（公告）日：2020-11-24

  本发明公开了一种4‑Boc‑2,5,6,7‑四氢吡唑并[4,3‑b]吡啶及其衍生物的合成方法。该方法包含缩合反应和环化反应。缩合反应以式I(N‑Boc‑3‑哌啶酮或其衍生物)为底物，以N,N‑二甲基甲酰胺二甲基缩醛为缩合剂和溶剂，在85℃进行反应而得到结构式II所示的缩合产物。之后以式II与水合肼为底物，加入水合肼后搅拌，在85℃进行反应得到式III所示化合物4‑Boc‑2,5,6,7‑四氢吡唑并[4,3‑b]吡啶及其衍生物。该方法相对旧路线更经济，底物N‑Boc‑3‑哌啶酮或其衍生物、N,N‑二甲基甲酰胺二甲基缩醛和水合肼均非常廉价，而目标产物是昂贵且有高附加值；两个步骤的反应体系均非常简单，操作便捷也易分离；不涉及高压氢化，相比于旧路线安全性更好。
• TLR7/8 antagonists and uses thereof
  申请人：Merck Patent GmbH

  公开号：US10947214B2

  公开（公告）日：2021-03-16

  The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TLR7/8 antagonists.

  本发明涉及式 I 的化合物 及其药学上可接受的组合物，可用作 TLR7/8 拮抗剂。
• TLR7/8 ANTAGONISTS AND USES THEREOF
  申请人：Merck Patent GmbH

  公开号：US20180037570A1

  公开（公告）日：2018-02-08

  The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TLR7/8 antagonists.
• HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS
  申请人：THE UNIVERSITY OF SHEFFIELD

  公开号：US20220023281A1

  公开（公告）日：2022-01-27

  Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein HET, R 1 , R 2 , R 3 , R 4 , R 5 , L, L 1 , X 1 , X 2 , X 3 and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM 2 ). Also disclosed are the compounds for use in the treatment of diseases modulated AM 2 , including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.