3-(氨基甲基)-5,6-二甲基-2(1H)-吡嗪酮 | 501022-77-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 3-(氨基甲基)-5,6-二甲基-2(1H)-吡嗪酮
• 英文名称: 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one
• 英文别名: 3-(Aminomethyl)-5,6-dimethylpyrazin-2(1H)-one；3-(aminomethyl)-5,6-dimethyl-1H-pyrazin-2-one
• CAS: 501022-77-1
• 化学式: C₇H₁₁N₃O
• 分子量: 153.184
• InChiKey: AFGKJRZJOQCYOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-Boc-2,6-二甲基-L-酪氨酸 、 3-(氨基甲基)-5,6-二甲基-2(1H)-吡嗪酮 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成
  参考文献：
  名称：

  Design and synthesis of opioidmimetics containing 2′,6′-dimethyl-l-tyrosine and a pyrazinone-ring platform

  摘要：

  Twelve 2 ',6 '-dimethyl-L-tyrosine (Dmt) analogues linked to a pyrazinone platform were synthesized as 3- or 6-[H-Dmt-NH(CH2)(n)],3- or 6-R-2(1H)-pyrazinone (n = 1-4). 3-[H-Dmt-NH-(CH2)(4)]-6-beta-phenethyl-5-methyl-2(1H)-pyrazinone 11 bound to mu-opioid receptors with high affinity (K-i mu = 0.13 nM; Ki delta/K-i mu = 447) with mu-agonism (GPI IC50 = 15.9 nM) and weak delta-antagonism (MVD pA(2) = 6.35), Key factors affecting opioid affinity and functional bioactivity are the length of the aminoalkyl chain linked to Dmt and the nature of the R residue. These data present a simplified method for the formation of pyrazinone opioidmimetics and new lead compounds. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.08.058
• 作为产物：
  描述：

  {2-[1-(Benzyloxycarbonylamino-methyl)-3-chloro-2-oxo-propylcarbamoyl]-2-tert-butoxycarbonylamino-ethyl}-carbamic acid benzyl ester 在 钯 1,4-二氧六环 、 盐酸 、 氢气 作用下， 以 甲醇 、 水 、 溶剂黄146 为溶剂， 反应 1.17h， 生成 3-(氨基甲基)-5,6-二甲基-2(1H)-吡嗪酮
  参考文献：
  名称：

  Immediate deamination from the aminomethyl group attached to 1,2-dihydropyrazin-2-one derivative during catalytic hydrogenation

  摘要：

  The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove benzyloxycarbonyl (Z) groups resulted ill a side reaction. Purification by reverse-phase HPLC and analysis by proton unclear magnetic resonance (H-1 NMR) spectroscopy identified the product as 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. It was determined through the synthesis of two 1,2-dihydropyrazin-2-one derivatives, composed of alanine and 2,3-diaminopropionic acid that deamination occurred specifically and easily (under atmospheric pressure and at the room temperature) Only in the case of 6-benzyloxycarbonylaminomethyl-3,5-dimethyl-1,2-dihydropyrazin-2-one. The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one specifically yields the deaminated product, 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)01944-5

文献信息

• Studies on the Mechanism of 1,2-Dihydropyrazin-2-one Ring Formation from Dipeptidyl Chloromethyl Ketone and Its Chemical Properties: Immediate Deamination during Catalytic Hydrogenation
  作者：Anna Miyazaki、Yutaka Fujisawa、Kimitaka Shiotani、Yoshio Fujita、Tingyou Li、Yuko Tsuda、Toshio Yokoi、Sharon D. Bryant、Lawrence H. Lazarus、Yoshio Okada

  DOI：10.1248/cpb.53.1152

  日期：——

  1,2-Dihydropyrazin-2-one derivatives, which have two aminoalkyl groups at the positions 3 and 6, were found to be efficient tools for the construction of potent, selective and long-acting opioid mimetics. During the course of preparation, we found that the catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove the benzyloxycarbonyl groups resulted in a side reaction. By MS and NMR studies and by preparation of additional 1,2-dihydropyrazin-2-one derivatives, the structure of the by-product was identified as 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. Preparation of additional compounds substituted with deuterium provided us with sufficient information to confirm the structure of the product and to support a cyclization mechanism in its formation.

  在3和6位具有两个氨基烷基团的1,2-二氢吡嗪-2-酮衍生物被发现是构建强效、选择性和长效类吗啡模拟物的有效工具。在准备过程中，我们发现3,6-双(苄氧羰基氨基甲基)-5-甲基-1,2-二氢吡嗪-2-酮的催化氢化以去除苄氧羰基基团导致了副反应。通过质谱和核磁共振研究以及制备额外的1,2-二氢吡嗪-2-酮衍生物，副产物的结构被鉴定为3-氨基甲基-5,6-二甲基-1,2-二氢吡嗪-2-酮。制备含有氘的额外化合物为我们提供了足够的信息以确认产物的结构并支持其形成的环化机制。
• Design and synthesis of opioidmimetics containing 2′,6′-dimethyl-l-tyrosine and a pyrazinone-ring platform
  作者：Kimitaka Shiotani、Tingyou Li、Anna Miyazaki、Yuko Tsuda、Toshio Yokoi、Akihiro Ambo、Yusuke Sasaki、Sharon D. Bryant、Lawrence H. Lazarus、Yoshio Okada

  DOI：10.1016/j.bmcl.2007.08.058

  日期：2007.11

  Twelve 2 ',6 '-dimethyl-L-tyrosine (Dmt) analogues linked to a pyrazinone platform were synthesized as 3- or 6-[H-Dmt-NH(CH2)(n)],3- or 6-R-2(1H)-pyrazinone (n = 1-4). 3-[H-Dmt-NH-(CH2)(4)]-6-beta-phenethyl-5-methyl-2(1H)-pyrazinone 11 bound to mu-opioid receptors with high affinity (K-i mu = 0.13 nM; Ki delta/K-i mu = 447) with mu-agonism (GPI IC50 = 15.9 nM) and weak delta-antagonism (MVD pA(2) = 6.35), Key factors affecting opioid affinity and functional bioactivity are the length of the aminoalkyl chain linked to Dmt and the nature of the R residue. These data present a simplified method for the formation of pyrazinone opioidmimetics and new lead compounds. (c) 2007 Elsevier Ltd. All rights reserved.
• Immediate deamination from the aminomethyl group attached to 1,2-dihydropyrazin-2-one derivative during catalytic hydrogenation
  作者：Yoshio Okada、Yutaka Fujisawa、Akihisa Morishita、Kimitaka Shiotani、Anna Miyazaki、Yoshio Fujita、Tingyou Li、Yuko Tsuda、Toshio Yokoi、Sharon D. Bryant、Lawrence H. Lazarus

  DOI：10.1016/s0040-4039(02)01944-5

  日期：2002.11

  The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove benzyloxycarbonyl (Z) groups resulted ill a side reaction. Purification by reverse-phase HPLC and analysis by proton unclear magnetic resonance (H-1 NMR) spectroscopy identified the product as 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. It was determined through the synthesis of two 1,2-dihydropyrazin-2-one derivatives, composed of alanine and 2,3-diaminopropionic acid that deamination occurred specifically and easily (under atmospheric pressure and at the room temperature) Only in the case of 6-benzyloxycarbonylaminomethyl-3,5-dimethyl-1,2-dihydropyrazin-2-one. The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one specifically yields the deaminated product, 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. (C) 2002 Elsevier Science Ltd. All rights reserved.