tert-butyl (2R,3aR,6aR)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)-octahydropentalen-2-yl-carbamate | 1422436-98-3

• 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: tert-butyl (2R,3aR,6aR)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)-octahydropentalen-2-yl-carbamate
• 英文别名: tert-butyl N-[(2R,3aR,6aR)-6a-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridine-6-carbonyl]-2,3,3a,4,5,6-hexahydro-1H-pentalen-2-yl]carbamate
• CAS: 1422436-98-3
• 化学式: C₂₃H₃₀F₃N₃O₃
• 分子量: 453.505
• InChiKey: BKBRZCOSQKKMGU-ZDPZECHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R,3aR,6aR)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)-octahydropentalen-2-yl-carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 ((2R,3aR,6aR)-2-aminooctahydropentalen-3a-yl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone
  参考文献：
  名称：

  Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists

  摘要：

  Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a-carboxamide scaffold were designed. SAR studies led to a series of potent compounds. For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice. In addition, an asymmetric synthesis to the core structures was developed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.069
• 作为产物：
  描述：

  (2R,3aR,6aR)-methyl 2-(bis(tert-butoxycarbonyl)amino)-5-methyleneoctahydropentalene-3a-carboxylate 在 水 、 1-羟基苯并三唑 、 臭氧 、 sodium sulfate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 对甲苯磺酰肼 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 tert-butyl (2R,3aR,6aR)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)-octahydropentalen-2-yl-carbamate
  参考文献：
  名称：

  Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists

  摘要：

  Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a-carboxamide scaffold were designed. SAR studies led to a series of potent compounds. For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice. In addition, an asymmetric synthesis to the core structures was developed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.069

文献信息

• Lab-Scale Preparation of a Novel Carbocyclic Chemokine Receptor Antagonist
  作者：Christopher A. Teleha、Shawn Branum、Yongzheng Zhang、Michael E. Reuman、Luc Van Der Steen、Marc Verbeek、Nagy Fawzy、Gregory C. Leo、Fu-An Kang、Chaozhong Cai、Michael Kolpak、Derek A. Beauchamp、Mark J. Wall、Ronald K. Russell、Zhihua Sui、Hilde Vanbaelen

  DOI：10.1021/op500265z

  日期：2014.12.19

  preparation of a novel chemokine receptor type 2 (CCR-2) antagonist is described on a 135 g scale. The synthesis of an all-carbon bicyclic core was accomplished using a radical cyclization strategy using chiral precursors, wherein elaboration led to N-Boc carboxylic acid in good yield. After amidation using a traditional coupling reaction, a reductive amination using enantiomerically enriched 3-methoxy-4-pyranone

  新型的2型趋化因子受体（CCR-2）拮抗剂的制备以135 g规模进行了描述。全碳双环核的合成是通过使用手性前体的自由基环化策略完成的，其中精细化导致N-Boc羧酸收率好。使用传统的偶联反应进行酰胺化后，使用对映异构体富集的3-甲氧基-4-吡喃酮进行还原胺化反应，生成最终化合物。尽管合成的几个步骤涉及试剂，这些试剂在工艺中不是优选的方法，并且色谱法可用于提供最终琥珀酸盐的游离碱非对映异构体，但整个途径都经过了稳定的中间体，可用于将来的规模化生产。这种实验室规模的综合在快速扩大规模和对所有可能的方法和途径进行更彻底的过程审查之间取得了平衡。
• Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists
  作者：Chaozhong Cai、Fu-An Kang、Cuifen Hou、John C. O’Neill、Evan Opas、Sandra McKenney、Dana Johnson、Zhihua Sui

  DOI：10.1016/j.bmcl.2012.10.069

  日期：2013.1

  Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a-carboxamide scaffold were designed. SAR studies led to a series of potent compounds. For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice. In addition, an asymmetric synthesis to the core structures was developed. (C) 2012 Elsevier Ltd. All rights reserved.