2-phenyl-5,6,7,8-tetrahydroquinazolin-4(3H)-one | 34127-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-phenyl-5,6,7,8-tetrahydroquinazolin-4(3H)-one
• 英文别名: 2-phenyl-5,6,7,8-tetrahydro-3H-quinazolin-4-one
• CAS: 34127-13-4
• 化学式: C₁₄H₁₄N₂O
• mdl: MFCD00445592
• 分子量: 226.278
• InChiKey: UICMJIZPQLNBRS-UHFFFAOYSA-N

物化性质

• 熔点：
  238-239 °C
• 沸点：
  386.2±25.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.285
• 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-5,6,7,8-tetrahydroquinazolin-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 17.0h， 生成 ethyl 2-[4-[(2-phenyl-5,6,7,8-tetrahydroquinazolin-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-氧代-环己烷羧酰胺 在 palladium on activated charcoal ammonium hydroxide 作用下， 以 硝基苯 为溶剂， 反应 0.5h， 生成 2-phenyl-5,6,7,8-tetrahydroquinazolin-4(3H)-one
  参考文献：
  名称：

  Fueloep, Ferenc; Bernath, Gabor, Heterocycles, 1985, vol. 23, # 12, p. 3095 - 3098

  摘要：

  DOI：

文献信息

• Access to Variously Substituted 5,6,7,8-Tetrahydro-3H-quinazolin-4-ones via Diels–Alder Adducts of Phenyl Vinyl Sulfone to Cyclobutene-Annelated Pyrimidinones
  作者：Suryakanta Dalai、Vladimir N. Belov、Shamil Nizamov、Karsten Rauch、Dirk Finsinger、Armin de Meijere

  DOI：10.1002/ejoc.200600060

  日期：2006.6

  elimination of methanol to afford the cyclobutene-annelated pyrimidinones 6 in 43–83 % yield (7 examples). Thermal cyclobutene-ring opening of the latter at 175 °C followed by regioselective Diels–Alder cycloaddition with phenyl vinyl sulfone gives the 2-aryl-6-(phenylsulfonyl)-5,6,7,8-tetrahydroquinazolinone derivatives 12 in 39–83 % yield (7 examples). Base-induced elimination of benzenesulfinic acid and subsequent

  在碱性条件下（Et3N，二恶烷），芳香脒 4 和 S-甲基异硫脲 4g 干净地进行迈克尔加成到 2-氯-2-环亚丙基乙酸甲酯（5），然后是分子内亲核取代，环丙基到环丁基环扩大，去质子化和环化反应消除甲醇，以 43-83% 的产率得到环丁烯退火的嘧啶酮 6（7 个例子）。后者在 175 °C 下热环丁烯开环，然后与苯基乙烯基砜进行区域选择性 Diels-Alder 环加成，得到 2-芳基-6-（苯基磺酰基）-5,6,7,8-四氢喹唑啉酮衍生物 12 in 39-83 % 产率（7 个例子）。碱诱导的苯亚磺酸消除和随后的催化氢化导致 2-芳基四氢喹唑啉酮衍生物 14 以优异的产率（6 个例子）。在磺酰基取代的中心去质子化、烷基化和随后消除苯亚磺酸，然后催化氢化得到 2,6-二取代的四氢喹唑啉酮 17a-R。用仲胺对 12g 中的甲硫基进行亲核取代产生 2-（二烷基氨基）四氢喹唑啉酮 14i–k。（©
• 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。
• Fe₃O₄nanoparticle-supported copper(I): magnetically recoverable and reusable catalyst for the synthesis of quinazolinones and bicyclic pyrimidinones
  作者：Lin Yu、Min Wang、Pinhua Li、Lei Wang

  DOI：10.1002/aoc.2902

  日期：2012.11

  A highly efficient, easily recoverable and reusable Fe3O4 magnetic nanoparticle‐supported Cu(I) catalyst has been developed for the synthesis of quinazolinones and bicyclic pyrimidinones. In the presence of supported Cu(I) catalyst (10 mol%), amidines reacted with substituted 2‐halobenzoic acids and 2‐bromocycloalk‐1‐enecarboxylic acids to generate the corresponding N‐heterocycle products in good to

  已经开发出了一种高效，易于回收和可重复使用的Fe 3 O 4磁性纳米粒子负载的Cu（I）催化剂，用于合成喹唑啉酮和双环嘧啶酮。在负载型Cu（I）催化剂（10 mol％）的存在下，am与取代的2-卤代苯甲酸和2-溴代环烷基-1-烯羧酸反应生成相应的N杂环产物，在室温下室温下具有良好或优异的收率。 DMF。另外，负载的Cu（I）催化剂可被回收至少10次而不会显着损失其催化活性。版权所有©2012 John Wiley＆Sons，Ltd.
• Synthesis and biological evaluation of novel 6,7-dihydro-5H-cyclopenta[d]pyrimidine and 5,6,7,8-tetrahydroquinazoline derivatives as sigma-1 (σ1) receptor antagonists for the treatment of pain
  作者：Yu Lan、Yiyan Songyang、Lingli Zhang、Yan Peng、Jinchun Song

  DOI：10.1016/j.bmcl.2016.02.077

  日期：2016.4

  The synthesis and biological evaluation of new series of 6,7-dihydro-5H-cyclopenta[d]pyrimidine and 5,6,7,8-tetrahydroquinazoline derivatives as selective sigma-1 receptor (σ1R) antagonists are reported. The receptor affinities of new compounds were evaluated in vitro in σ1 and σ2 receptor binding assays. The structure-active relationship study leads us to the most promising compound: 2-(4-chlorop

  的合成和新系列6,7-二氢5的生物学评价ħ环戊二烯并[ d（]嘧啶和5,6,7,8-四氢喹唑啉衍生物作为选择性σ-1受体σ 1个R）报道拮抗剂。新化合物的受体亲和力在体外进行了评价σ 1和σ 2受体结合试验。通过结构-活性关系研究，我们得出了最有希望的化合物：2-（4-氯苯基）-4-（3-（4-甲基哌啶-1-基）丙氧基）-5,6,7,8-四氢喹唑啉（33）。化合物33具有用于施加纳摩尔亲和力σ 1个R（ķ我σ1  = 15.6 1nM）和高σ 1 / σ 2选择性（ķ我σ 2 > 2000纳米），和鉴定为σ 1 - [R拮抗剂。在动物模型中，化合物33在福尔马林试验中表现出剂量依赖性的抗伤害感受作用。这些结果表明，化合物33可能是用于疼痛治疗的有效止痛药。
• 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。