2-phenyl-5,6-pentamethylenepyrimidin-4(3H)-one | 91272-15-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-phenyl-5,6-pentamethylenepyrimidin-4(3H)-one
• 英文别名: 2-phenyl-6,7,8,9-tetrahydro-3H-cyclohepta[d]pyrimidin-4(5H)-one；2-Phenyl-3,5,6,7,8,9-hexahydrocyclohepta[d]pyrimidin-4-one；2-phenyl-3,5,6,7,8,9-hexahydrocyclohepta[d]pyrimidin-4-one
• CAS: 91272-15-0
• 化学式: C₁₅H₁₆N₂O
• mdl: MFCD19384930
• 分子量: 240.305
• InChiKey: OVHYQRNWBRPWCB-UHFFFAOYSA-N

物化性质

• 熔点：
  237-239 °C
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-phenyl-5,6-pentamethylenepyrimidin-4(3H)-one 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 ethyl 2-[4-[(2-phenyl-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-4-yl)amino]phenyl]acetate
  参考文献：
  名称：

  Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors

  摘要：

  2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d] pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d] pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50 = 25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50 = 7.5 nM) and TNF-alpha production in mouse splenocytes (IC50 = 9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.104
• 作为产物：
  描述：

  2-bromo-cyclohept-1-enecarboxylic acid 、 苄脒盐酸盐 在 copper(l) iodide 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 以75%的产率得到2-phenyl-5,6-pentamethylenepyrimidin-4(3H)-one
  参考文献：
  名称：

  在温和条件下简便高效的铜催化合成双环嘧啶酮

  摘要：

  已经开发了一种简单有效的铜催化方法，用于在温和条件下合成含有六、七、八元环的双环嘧啶酮。该方案以易得的2-溴环烷-1-烯羧酸、ids、脒和胍为起始原料，铜催化级联偶联提供相应的双环嘧啶酮，无需添加任何配体或添加剂，该方法具有经济性和实用的优势。

  DOI：

  10.1055/s-0030-1258803

文献信息

• Easy and Efficient Copper-Catalyzed Synthesis of Bicyclic Pyrimidinones under Mild Conditions
  作者：Hua Fu、Qi Guo、Haijun Yang、Hongxia Liu、Yuyang Jiang

  DOI：10.1055/s-0030-1258803

  日期：2010.10

  A simple and efficient copper-catalyzed method has been developed for synthesis of bicyclic pyrimidinones containing six-, seven-, eight-membered rings under mild conditions. The protocol uses readily available 2-bromocycloalk-1-enecarboxylic ac- , ids, amidines, and guanidines as the starting materials, copper-catalyzed cascade couplings provide the corresponding bicyclic pyrimidinones without addition

  已经开发了一种简单有效的铜催化方法，用于在温和条件下合成含有六、七、八元环的双环嘧啶酮。该方案以易得的2-溴环烷-1-烯羧酸、ids、脒和胍为起始原料，铜催化级联偶联提供相应的双环嘧啶酮，无需添加任何配体或添加剂，该方法具有经济性和实用的优势。
• Bernath, G.; Lazar, J.; Gera, L., Acta Chimica Hungarica, 1984, vol. 115, # 3, p. 231 - 236
  作者：Bernath, G.、Lazar, J.、Gera, L.、Goendoes, Gy.、Ecsery, Z.

  DOI：——

  日期：——
• BERNATH, G.;LAZAR, J.;GERA, L.;GOENDOES, GY.;ECSERY, Z., ACTA CHIM. HUNG., 1984, 115, N 3, 231-235
  作者：BERNATH, G.、LAZAR, J.、GERA, L.、GOENDOES, GY.、ECSERY, Z.

  DOI：——

  日期：——
• Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors
  作者：Taiji Goto、Akiko Shiina、Toshiharu Yoshino、Kiyoshi Mizukami、Kazuki Hirahara、Osamu Suzuki、Yoshitaka Sogawa、Tomoko Takahashi、Tsuyoshi Mikkaichi、Naoki Nakao、Mizuki Takahashi、Masashi Hasegawa、Shigeki Sasaki

  DOI：10.1016/j.bmcl.2013.03.104

  日期：2013.6

  2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d] pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d] pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50 = 25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50 = 7.5 nM) and TNF-alpha production in mouse splenocytes (IC50 = 9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex. (C) 2013 Elsevier Ltd. All rights reserved.
• Microwave-Assisted Copper-Powder-Catalyzed Synthesis of Pyrimidinones from β-Bromo α,β-Unsaturated Carboxylic Acids and Amidines
  作者：Chan Cho、Son Ho

  DOI：10.1055/s-0033-1340283

  日期：——

  β-Bromo α,β-unsaturated carboxylic acids were coupled and cyclized with amidine hydrochlorides by microwave irradiation in the presence of catalytic amounts of copper powder and a base to give the corresponding pyrimidinones in high yields.

  在催化量的铜粉和碱存在下，通过微波辐射将β-溴α,β-不饱和羧酸与脒盐酸盐偶联并环化，以高产率得到相应的嘧啶酮。