6-苄基-2-甲基-5,6,7,8-四氢吡啶并[4,3-D]嘧啶-4(3H)-酮 | 1448-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 6-苄基-2-甲基-5,6,7,8-四氢吡啶并[4,3-D]嘧啶-4(3H)-酮
• 英文名称: 6-benzyl-2-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol
• 英文别名: 6-benzyl-2-methyl-5,6,7,8-tetrahydro-3H-pyrido[4,3-d]pyrimidin-4-one；6-benzyl-2-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one；6-benzyl-2-methyl-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one
• CAS: 1448-40-4
• 化学式: C₁₅H₁₇N₃O
• mdl: MFCD06776713
• 分子量: 255.319
• InChiKey: IGVWHXWXRQGWDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-苄基-2-甲基-5,6,7,8-四氢吡啶并[4,3-D]嘧啶-4(3H)-酮 在 三氯氧磷 作用下， 反应 5.0h， 以71%的产率得到6-benzyl-4-chloro-2-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine
  参考文献：
  名称：

  Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators

  摘要：

  Based on the approach of merged pharmacophores of GPR119 agonists and DPP-4 inhibitors, a series of tetrahydropyridopyrimidine compounds were designed as dual GPR119 and DPP-4 modulators with hypoglycemic activity. Seven fragments extracted from DPP-4 inhibitors were hybridized with the scaffold of tetrahydropyridopyrimidine. Among them, compound 51 displayed most potent GPR119 agonistic activity (EC50, = 8.7 nM) and good inhibition rate of 74.5% against DPP-4 at 10 mu M. Furthermore, the blood glucose AUC(0-2h) of 51 was reduced to 19.5% in the oral glucose tolerance test (oGTT) at the dose of 30 mg/kg in C57BL/6N mice, which was more potent than that of vildagliptin (16.4%) at the same dose. The docking study of compound 51 with DPP-4 indicated GPR119 agonists could inhibit DPP-4 to serve as dual GPR119 and DPP-4 modulators.

  DOI：

  10.1016/j.bioorg.2019.103390
• 作为产物：
  描述：

  3-[苄基-(2-甲氧基羰基乙基)-氨基]-丙酸乙酯 在 sodium methylate 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 15.0h， 生成 6-苄基-2-甲基-5,6,7,8-四氢吡啶并[4,3-D]嘧啶-4(3H)-酮
  参考文献：
  名称：

  饱和杂环，第172部分†。2,6-二取代的5,6,7,8-四氢吡啶并[4,3- d ]嘧啶衍生物的合成

  摘要：

  通过将丙烯酸甲酯添加到苄胺或α-氨基吡啶上，合成标题化合物，得到相应的二酯，例如。12，然后由后者进行Dieckmann缩合，得到酮酯13，将其与am和胍3，14缩合。通过氢解除去苄基并随后将所得化合物5中6位的氮原子烷基化，同时改变C-2上的取代基，得到了许多具有潜在生物学作用的产物；其中一些具有止痛和抗炎作用。

  DOI：

  10.1002/jhet.5570270708

文献信息

• Saturated heterocycles, Part 172. Synthesis of 2,6-disubstituted-5,6,7,8-tetrahydropyrido[4,3-<i>d</i>]pyrimidine derivatives
  作者：János Lázár、Gábor Bernáth

  DOI：10.1002/jhet.5570270708

  日期：1990.11

  The title compounds were synthesized via the addition of methyl acrylate to benzylamine or to α-aminopyridine, which gave the corresponding diesters, e.g. 12, followed by Dieckmann condensation of the latter to yield the keto-esters 13, which were condensed with amidines and guanidines, 3, 14. Removal of the benzyl group by hydrogenolysis and subsequent alkylation of the nitrogen atom at position 6

  通过将丙烯酸甲酯添加到苄胺或α-氨基吡啶上，合成标题化合物，得到相应的二酯，例如。12，然后由后者进行Dieckmann缩合，得到酮酯13，将其与am和胍3，14缩合。通过氢解除去苄基并随后将所得化合物5中6位的氮原子烷基化，同时改变C-2上的取代基，得到了许多具有潜在生物学作用的产物；其中一些具有止痛和抗炎作用。
• Tetrahydropyridine (THP) ring expansion under the action of activated terminal alkynes. The first synthesis and X-ray crystal structure of tetrahydropyrimido[4,5-d]azocines
  作者：Leonid G. Voskressensky、Tatiana N. Borisova、Innokenti S. Kostenev、Larisa N. Kulikova、Alexey V. Varlamov

  DOI：10.1016/j.tetlet.2005.11.136

  日期：2006.2

  Tetrahydropyridopyrimidines (THPPm) 1–3 underwent tandem cleavage–cyclization piperidine ring enlargement under the action of terminal activated alkynes to produce tetrahydropyrimido[4,5-d]azocines 4–7 in good preparative yields. The latter compounds are representatives of a new heterocyclic system.

  Tetrahydropyridopyrimidines（THPPm）1 - 3后行串联切割环化终端而激活炔以产生四氢嘧啶并[4,5-的作用下哌啶环放大d ] azocines 4 - 7中制备好的产率。后一种化合物是新杂环系统的代表。
• Transformations of tetrahydrobenzo[b][1,6]naphthyridines and tetrahydropyrido[4,3-b]pyrimidines under the action of dimethyl acetylene dicarboxylate
  作者：Leonid G. Voskressensky、Tatiana N. Borisova、Innokenti S. Kostenev、Ilia V. Vorobiev、Alexey V. Varlamov

  DOI：10.1016/j.tetlet.2005.02.001

  日期：2005.3

  6]naphthyridines 3, 4 undergo addition of DMAD, followed by a Stevens rearrangement of the intermediate ylide to yield methyl dioates 8 and 9. An alternative transformation sequence starts with migration of the dimethyl butenedioate anion to the carbon of the CN group, followed by the addition of 1 mol of water, to provide succinates 10 and 11. In contrast, tetrahydropyrido[4,3-b]pyrimidines 5–7 undergo a tandem

  10 Cyanotetrahydrobenzo [ b ] [1,6]萘啶3，4进行加成DMAD，随后通过中间叶立德的史蒂文斯重排，得到甲基dioates 8和9。替代的转化顺序以丁烯二酸二甲酯的阴离子向CN基团的碳迁移开始，然后加入1摩尔水，以生成琥珀酸酯10和11。相反，四氢吡啶并[4,3- b ]嘧啶5 – 7经历一分子溶剂的串联裂解过程。生成的烯胺很容易被强酸裂解，得到二氢嘧啶基乙胺，而该胺几乎不能通过其他合成方法获得。
• WO2008/130584
  申请人：——

  公开号：——

  公开（公告）日：——
• Huber, Imre; Fueloep, Ferenc; Lazar, Janos, Journal of the Chemical Society. Perkin transactions I, 1992, # 1, p. 157 - 162
  作者：Huber, Imre、Fueloep, Ferenc、Lazar, Janos、Bernath, Gabor、Toth, Gabor

  DOI：——

  日期：——