6-Chloro-5-fluoro-1-[(4-methoxyphenyl)methyl]-4-(trifluoromethyl)quinazolin-2-one | 1380540-11-3

• 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: 6-Chloro-5-fluoro-1-[(4-methoxyphenyl)methyl]-4-(trifluoromethyl)quinazolin-2-one
• 英文别名: 6-chloro-5-fluoro-1-[(4-methoxyphenyl)methyl]-4-(trifluoromethyl)quinazolin-2-one
• CAS: 1380540-11-3
• 化学式: C₁₇H₁₁ClF₄N₂O₂
• 分子量: 386.733
• InChiKey: HDMAJVWXOXXELG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3-丁二烯酸乙酯 、 6-Chloro-5-fluoro-1-[(4-methoxyphenyl)methyl]-4-(trifluoromethyl)quinazolin-2-one 在 吡啶 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以96%的产率得到ethyl 2-(6-chloro-5-fluoro-1-(4-methoxybenzyl)-2-oxo-4-(trifluoromethyl)-1,2,3,4-tetrahydroquinazolin-4-yl)buta-2,3-dienoate
  参考文献：
  名称：

  Nucleophilic Lewis Base Dependent Addition Reactions of Allenoates with Trifluoromethylated Cyclic Ketimines

  摘要：

  A detailed investigation on the different reactivity patterns shown by phosphorus- and nitrogen-containing Lewis base catalysts in the reactions of allenoates with cyclic trifluoromethyl ketimines was accomplished. With PPh3, [3 + 2] annulations proceeded smoothly to afford dihydropyrrole derivatives in excellent yields. Under the catalysis of DABCO, [2 + 2] annulations occurred, producing azetidine derivatives in good to high yields. However, in the presence of pyridine, alpha,alpha'-disubstituted allenoates were obtained in very high yields via aza-Morita-Baylis-Hillman reactions. These studies provide an opportunity for diverse synthesis of a variety of N-heterocyclic compounds from the same starting materials.

  DOI：

  10.1021/jo500356t

文献信息

• Highly Enantioselective Decarboxylative Mannich Reaction of Malonic Acid Half Oxyesters with Cyclic Trifluoromethyl Ketimines: Synthesis of β-Amino Esters and Anti-HIV Drug DPC 083
  作者：Hai-Na Yuan、Shen Li、Jing Nie、Yan Zheng、Jun-An Ma

  DOI：10.1002/chem.201303307

  日期：2013.11.18

  An organocatalytic enantioselective decarboxylative Mannich reaction of malonic acid half oxyesters with cyclic ketimines was developed for the preparation of enantioenriched β‐amino esters with a quaternary stereogenic center and the anti‐HIV drug DPC 083 (see scheme).

  开发了丙二酸半含氧酸酯与环状酮亚胺的有机催化对映选择性脱羧曼尼希反应，用于制备具有季立体位中心和抗HIV药物DPC 083的对映体富集的β-氨基酯（参见方案）。
• Zinc-mediated enantioselective addition of terminal 3-en-1-ynes to cyclic trifluoromethyl ketimines
  作者：Yue Zhang、Jing Nie、Fa-Guang Zhang、Jun-An Ma

  DOI：10.1016/j.jfluchem.2018.01.008

  日期：2018.4

  A facile enantioselective addition of terminal 3-en-1-ynes to cyclic N-acyl trifluoromethyl ketimines is reported. In the presence of Zinc/BINOL complexes, a series of enynylated tertiary carbinamines were readily obtained in 90–97% yield with 70–97% enantiomeric excess in a single chemical operation under mild reaction conditions.

  据报道，在环N-酰基三氟甲基酮亚胺中容易地对末端3-烯-1-炔进行对映选择性加成。在锌/ BINOL复合物的存在下，在温和的反应条件下，一次化学操作即可轻松获得一系列烯化的叔卡宾胺，产率为90-97％，对映体过量为70-97％。
• Enantioselective Diynylation of Cyclic N-Acyl Ketimines: Access to Chiral Trifluoromethylated Tertiary Carbinamines
  作者：Fa-Guang Zhang、Hai Ma、Jing Nie、Yan Zheng、Qingzhi Gao、Jun-An Ma

  DOI：10.1002/adsc.201100926

  日期：2012.5.21

  A novel enantioselective diynylation of cyclic N‐acyl trifluoromethylketimines with chloramphenicol‐amine derivatives as chiral additives has been successfully developed. A series of diynylated tertiary trifluoromethylcarbinamines were obtained in high yields with good to excellent enantioselectivities (with up to 99% ee).

  已成功开发了一种新的对映选择性的环状N-酰基三氟甲基酮亚胺与氯霉素-胺衍生物作为手性添加剂的二炔基化反应。以高收率获得了一系列具有良好或优异对映选择性（高达99％ee）的二烷基化叔三氟甲基碳胺。
• Bisphosphine-Triggered One-Pot Sequential [3 + 2]/[3 + 2] Annulation of Allenoates with Cyclic Ketimines
  作者：Li-Jun Yang、Shuai Wang、Jing Nie、Shen Li、Jun-An Ma

  DOI：10.1021/ol402364t

  日期：2013.10.18

  bisphosphine-triggered one-pot sequential [3 + 2]/[3 + 2] annulation of allenoates with cyclic ketimines was developed, in which the product of the first [3 + 2] annulation is the electron-deficient substrate for the second [3 + 2] annulation reaction. The reaction is exceptionally regioselective and diastereoselective. This novel and highly convergent strategy may open up a new viewpoint in utilizing allenoates to prepare

  开发了一种高效的双膦触发的一锅式连续的[3 + 2] / [3 + 2]环烯丙酸酯与环酮亚胺环化反应，其中第一个[3 + 2]环化反应的产物是电子缺陷的底物。第二次[3 + 2]环化反应。该反应是区域选择性和非对映选择性的。这种新颖且高度收敛的策略可以为利用烯丙酸酯制备N-稠合多环化合物开辟新的观点。
• A Highly Regio- and Diastereoselective Phosphane-Catalyzed [3+2] Annulation of Morita-Baylis-Hillman Carbonates with Cyclic<i>N</i>-Acyl Ketimines
  作者：Li-Jun Yang、Hua Cai、Jing Nie、Jun-An Ma

  DOI：10.1002/ejoc.201300342

  日期：2013.7

  A highly regio- and diastereoselective phosphane-catalyzed [3+2] annulation of Morita–Baylis–Hillman (MBH) carbonates with cyclic N-acyl-substituted ketimines was developed. In the presence of the catalyst PBu3 (10 mol-%), a series of N-fused tricyclic products were obtained in excellent yields and diastereoselectivities under mild conditions. An example of a catalytic enantioselective annulation is

  开发了一种高度区域选择性和非对映选择性磷烷催化的 Morita-Baylis-Hillman (MBH) 碳酸酯与环状 N-酰基取代的酮亚胺的 [3+2] 环化。在催化剂 PBu3 (10 mol-%) 存在下，在温和条件下以优异的产率和非对映选择性获得了一系列 N-稠合三环产物。还介绍了催化对映选择性环化的一个例子。