3-氨基-4-吡啶基氨基甲酸甲酯 | 623562-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-氨基-4-吡啶基氨基甲酸甲酯
• 英文名称: 3-amino-4-pyridylcarbamic acid methyl ester
• 英文别名: methyl (3-aminopyridin-4-yl)carbamate；methyl 3-aminopyridin-4-yl carbamate；methyl N-(3-aminopyridin-4-yl)carbamate
• CAS: 623562-26-5
• 化学式: C₇H₉N₃O₂
• 分子量: 167.167
• InChiKey: WADZRHBGMFVDKY-UHFFFAOYSA-N

物化性质

• 熔点：
  124.0-126.0 °C(Solv: chloroform (67-66-3))
• 沸点：
  284.6±25.0 °C(Predicted)
• 密度：
  1.343±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  77.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-4-吡啶基氨基甲酸甲酯 在 硫酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 4.0h， 以99%的产率得到1H-1,2,3-噻唑并[4,5-c]吡啶
  参考文献：
  名称：

  1 H -1,2,3-三唑并-[4,5- c ]吡啶的N-酰基和N-烷氧基羰基衍生物；制备及应用

  摘要：

  研究了N-取代的1,2,3-三唑并[4,5- c ]吡啶1a-e的N-酰化和N-烷氧羰基化能力。易于制备烷氧基羰基三唑并吡啶衍生物（1c-e），产率为81-96％（相应的四氟硼酸酯> 95％）。通过形成氨基和氨基甲酸酯保护的伯胺衍生物，已证明三唑并[4，5- c ]吡啶（1）可作为良好的离去基团。该方法对于N-叔丁氧羰基（N-BOC）保护氨基酸，苯丙氨酸。一锅制备1a-e，然后与胺或氨基酸直接反应，可促进合成转化。因此，本方法提供了用于原位制备直接用于保护胺和氨基酸的三唑并吡啶试剂的有效且方便的方案。N-酰基和N-烷氧基羰基三唑并吡啶（1a-e）可以通过胺保护，吡啶硝化，硝基还原和重氮化/环化从4-氨基吡啶（4）分四步轻松制备。所有反应都在非常温和的条件下提供了高产率快速转化的优点。

  DOI：

  10.1002/jhet.5570430223
• 作为产物：
  描述：

  methyl 3-nitropyridin-4-yl carbamate 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 24.0h， 以98%的产率得到3-氨基-4-吡啶基氨基甲酸甲酯
  参考文献：
  名称：

  取代的1,3-二氢-2 H-咪唑并[4,5 - c ]吡啶-2-酮的制备

  摘要：

  研究了从4-氨基吡啶合成6-取代-咪唑并[4,5- c ]吡啶-2-酮的新途径。4-氨基吡啶保护成烷基氨基甲酸酯用五氧化二氮硝化相应的甲基，我丙基和吨丁基3-硝基吡啶-4-基氨基甲酸盐（5A-C在51-63％的产率）。尝试在由ONSH和VNS技术的6位来替代这些成功用丁基胺和吨丁基氨基甲酸酯9。由3-硝基吡啶-4-氨基甲酸叔丁酯5a，5c 1,3-二氢-2 H-咪唑并[4,5- c ]吡啶-2-一（1）分别以73％和39％的产率形成。叔丁基6 - N-丁基氨基-3氨基吡啶-4-氨基甲酸酯（6）得到6-丁基氨基-1,3-二氢-2 H-咪唑并[4,5 - c ]-吡啶-2-酮（7），产率为53％。

  DOI：

  10.1002/jhet.5570400405

文献信息

• 1,3-Dihydro-2<i>H</i>-imidazo[4,5-<i>c</i>]pyridin-2-one
  作者：Jarle Holt、Jan M. Bakke、Anne Fiksdahl

  DOI：10.1002/jhet.5570430341

  日期：2006.5

  A facile acid catalysed cyclisation method for the preparation of the cyclic urea 2H-imidazo[4,5-c]pyridin-2-one (2) in > 95 % yield is reported. The biologically active compound 2 can be obtained by heating (3-amino-4-pyridinyl)-carbamic acid methyl, ethyl or tert-butyl esters (1a-c) in sulfuric acid (0.1 %) or in aqueous HBF4 (3.5 equivalents) for 10 min. - 3 hrs at 90 °C. The corresponding microwave-promoted

  报道了一种简便的酸催化环化方法，用于制备环状尿素2 H-咪唑并[4,5 - c ]吡啶-2-酮（2），产率> 95％。可以通过在硫酸（0.1％）或HBF 4水溶液（3.5当量）中加热（3-氨基-4-吡啶基）-氨基甲酸甲酯，乙酯或叔丁酯（1a-c）来获得生物活性化合物2。）10分钟。-90°C下3小时。相应的微波促进（MW）反应在几分钟内提供了纯产物2。6-丁基氨基取代的类似物（2a通过2-（丁基氨基）-5-氨基-4-吡啶基氨基甲酸异丙酯（1d）的环化，通过MW辐射以99％的产率相应地获得）。通过调节pH获得产物2的定量沉淀。该过程表示无溶剂的，“绿色”用于制备方法2。
• Formulating a new basis for the treatment against botulinum neurotoxin intoxication: 3,4-Diaminopyridine prodrug design and characterization
  作者：Joseph S. Zakhari、Isao Kinoyama、Mark S. Hixon、Antonia Di Mola、Daniel Globisch、Kim D. Janda

  DOI：10.1016/j.bmc.2011.09.019

  日期：2011.11

  Botulism is a disease characterized by neuromuscular paralysis and is produced from botulinum neurotoxins (BoNTs) found within the Gram positive bacterium Clostridium botulinum. This bacteria produces the most deadliest toxin known, with lethal doses as low as 1 ng/kg. Due to the relative ease of production and transport, the use of these agents as potential bioterrorist weapons has become of utmost concern. No small molecule therapies against BoNT intoxication have been approved to date. However, 3,4-diaminopyridine (3,4-DAP), a potent reversible inhibitor of voltage-gated potassium channels, is an effective cholinergic agonist used in the treatment of neuromuscular degenerative disorders that require cholinergic enhancement. 3,4-DAP has also been shown to facilitate recovery of neuromuscular action potential post botulinum intoxication by blocking K(+) channels. Unfortunately, 3,4-DAP displays toxicity largely due to blood-brain-barrier (BBB) penetration. As a dual-action prodrug approach to cholinergic enhancement we have designed carbamate and amide conjugates of 3,4-DAP. The carbamate prodrug is intended to be a slowly reversible inhibitor of acetylcholinesterase (AChE) along the lines of the stigmines thereby allowing increased persistence of released acetylcholine within the synaptic cleft. As a secondary activity, cleavage of the carbamate prodrug by AChE will afford the localized release of 3,4-DAP, which in turn, will enhance the pre-synaptic release of additional acetylcholine. Being a competitive inhibitor with respect to acetylcholine, the activity of the prodrug will be greatest at the synaptic junctions most depleted of acetylcholine. Here we report upon the synthesis and biochemical characterization of three new classes of prodrugs intended to limit previously reported stability and toxicity issues. Of the prodrugs examined, compound 32, demonstrated the most clinically relevant half-life of 2.76 h, while selectively inhibiting AChE over butyrylcholinesterase-a plasma-based high activity esterase. Future in vivo studies could provide validation of prodrug 32 as a potential treatment against BoNT intoxication as well as other neuromuscular disorders. (C) 2011 Elsevier Ltd. All rights reserved.
• AMINOPYRIDINE COMPOUNDS AND THEIR USES
  申请人：Hudson Michael J.

  公开号：US20140024621A1

  公开（公告）日：2014-01-23

  The invention generally relates to aminopyridines and methods of use thereof. In certain embodiments, the invention provides an aminopyridine or a pharmaceutically-acceptable salt thereof, in which the aminopyridine or the salt thereof includes a cleavable functional group that substantially prevents extra-hepatic hydrolysis.
• <i>N</i>-acyl and<i>N</i>-alkoxycarbonyl derivatives of 1<i>H</i>-1,2,3-triazolo-[4,5-<i>c</i>]pyridine; Preparation and application
  作者：Jarle Holt、Anne Fiksdahl

  DOI：10.1002/jhet.5570430223

  日期：2006.3

  The synthetic transformations are facilitated by the one-pot preparation of 1a-e followed by the direct reaction with the amines or amino acid. The present method thus offers an efficient and convenient protocol for the in situ preparation of triazolopyridine reagents to be used directly for the protection of amines and amino acids. N-Acyl- and N-alkoxycarbonyl triazolopyridines (1a-e) were readily prepared

  研究了N-取代的1,2,3-三唑并[4,5- c ]吡啶1a-e的N-酰化和N-烷氧羰基化能力。易于制备烷氧基羰基三唑并吡啶衍生物（1c-e），产率为81-96％（相应的四氟硼酸酯> 95％）。通过形成氨基和氨基甲酸酯保护的伯胺衍生物，已证明三唑并[4，5- c ]吡啶（1）可作为良好的离去基团。该方法对于N-叔丁氧羰基（N-BOC）保护氨基酸，苯丙氨酸。一锅制备1a-e，然后与胺或氨基酸直接反应，可促进合成转化。因此，本方法提供了用于原位制备直接用于保护胺和氨基酸的三唑并吡啶试剂的有效且方便的方案。N-酰基和N-烷氧基羰基三唑并吡啶（1a-e）可以通过胺保护，吡啶硝化，硝基还原和重氮化/环化从4-氨基吡啶（4）分四步轻松制备。所有反应都在非常温和的条件下提供了高产率快速转化的优点。
• Preparation of substituted 1,3-dihydro-2<i>H</i>-imidazo[4,5-<i>c</i>]pyridin-2-ones
  作者：Jan M. Bakke、Hanna S. H. Gautun、Harald Svensen

  DOI：10.1002/jhet.5570400405

  日期：2003.7

  butyl-amine and the t-butyl carbamate 9. From the methyl or t-butyl 3-nitropyridin-4-yl carbamates 5a, 5c 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (1) was formed in 73 and 39 % yields, respectively. t-Butyl 6-N-butylamin-3-aminopyridin-4-yl carbamate (6) gave 6-butylamino-1,3-dihydro-2H-imidazo[4,5-c]-pyridin-2-one (7) in 53 % yield.

  研究了从4-氨基吡啶合成6-取代-咪唑并[4,5- c ]吡啶-2-酮的新途径。4-氨基吡啶保护成烷基氨基甲酸酯用五氧化二氮硝化相应的甲基，我丙基和吨丁基3-硝基吡啶-4-基氨基甲酸盐（5A-C在51-63％的产率）。尝试在由ONSH和VNS技术的6位来替代这些成功用丁基胺和吨丁基氨基甲酸酯9。由3-硝基吡啶-4-氨基甲酸叔丁酯5a，5c 1,3-二氢-2 H-咪唑并[4,5- c ]吡啶-2-一（1）分别以73％和39％的产率形成。叔丁基6 - N-丁基氨基-3氨基吡啶-4-氨基甲酸酯（6）得到6-丁基氨基-1,3-二氢-2 H-咪唑并[4,5 - c ]-吡啶-2-酮（7），产率为53％。