4-(4,4-difluorocyclohex-1-en-1-yl)morpholine | 1263082-54-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-(4,4-difluorocyclohex-1-en-1-yl)morpholine
• 英文别名: 4-(4,4-Difluorocyclohexen-1-yl)morpholine；4-(4,4-difluorocyclohexen-1-yl)morpholine
• CAS: 1263082-54-7
• 化学式: C₁₀H₁₅F₂NO
• 分子量: 203.232
• InChiKey: CFUPEYMETUZYCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4,4-difluorocyclohex-1-en-1-yl)morpholine 在 sodium tetrahydroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 5,5-difluoro-2-hydroxy-cyclohexanesulfonamide
  参考文献：
  名称：

  1,1-Dioxo-5,6-dihydro-[4,1,2]oxathiazines, a novel class of 11ß-HSD1 inhibitors for the treatment of diabetes

  摘要：

  Racemic cis-1,1-dioxo-5,6-dihydro-[4,1,2]oxathiazine derivative 4a was isolated as an impurity in a sample of a hit from a HTS campaign on 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). After separation by chiral chromatography the 4a-S, 8a-R enantiomer of compound 4a was identified as the true, potent enzyme inhibitor. The cocrystal structure of 4a with human and murine 11 beta-HSD1 revealed the unique binding mode of the oxathiazine series. SAR elucidation and optimization in regard to metabolic stability led to monocyclic tetramethyloxathiazines as exemplified by compound 21g. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.102
• 作为产物：
  描述：

  吗啉 、 4,4-二氟环已酮 以 甲苯 为溶剂， 反应 5.0h， 生成 4-(4,4-difluorocyclohex-1-en-1-yl)morpholine
  参考文献：
  名称：

  1,1-Dioxo-5,6-dihydro-[4,1,2]oxathiazines, a novel class of 11ß-HSD1 inhibitors for the treatment of diabetes

  摘要：

  Racemic cis-1,1-dioxo-5,6-dihydro-[4,1,2]oxathiazine derivative 4a was isolated as an impurity in a sample of a hit from a HTS campaign on 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). After separation by chiral chromatography the 4a-S, 8a-R enantiomer of compound 4a was identified as the true, potent enzyme inhibitor. The cocrystal structure of 4a with human and murine 11 beta-HSD1 revealed the unique binding mode of the oxathiazine series. SAR elucidation and optimization in regard to metabolic stability led to monocyclic tetramethyloxathiazines as exemplified by compound 21g. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.102

文献信息

• Scope and Mechanistic Studies on the Ruthenium-Catalyzed Multicomponent Deaminative C–H Coupling Reaction of Phenols with Aldehydes and Enamines for the Formation of Xanthene and Dioxacyclic Derivatives
  作者：Nuwan Pannilawithana、Mina Son、Donghun Hwang、Mu-Hyun Baik、Chae S. Yi

  DOI：10.1021/acscatal.3c01651

  日期：2023.7.7

  6-tetrachloro-1,2-benzoquinone (L1) has been found to mediate a multicomponent deaminative coupling reaction of phenols with aldehydes and enamines to form xanthene products. The multicomponent C–H coupling reaction of phenols with 2-hydroxybenzaldehydes and cyclic enamines efficiently installed the tricyclic 1,3-dioxacin derivatives, while the analogous coupling reaction of phenols with 2-hydroxybenzaldehydes

  由四核Ru-H 络合物 [(PCy 3 )(CO)RuH] 4 (O)(OH) 2 ( 1 ) 与 3,4,5,6-四氯-1,2-苯醌原位生成的催化体系（L1）已被发现介导酚与醛和烯胺的多组分脱氨偶联反应，形成呫吨产物。酚与2-羟基苯甲醛和环状烯胺的多组分C-H偶联反应有效地安装了三环1,3-二恶星衍生物，而酚与2-羟基苯甲醛和三乙胺的类似偶联反应选择性地形成双环1,5-二恶环衍生物。密度泛函理论 (DFT) 计算建立了两条能量上可行的呫吨产物形成机制途径，其中两条途径均将 C-O 键裂解步骤确定为周转限制步骤。3,5-二甲氧基苯酚与烯胺和对位取代苯甲醛偶联反应的哈米特图p -XC 6 H 4 CHO (X = OMe, Me, H, Cl, CF 3 ) 显示负斜率 (ρ = -0.98)。计算的能量分析显示通过 C-O 裂解速率限制步骤的机制具有类似的趋势 (ρ = -0.59)。实验和
• Concise synthesis of 2,3-disubstituted quinoline derivatives <i>via</i> ruthenium-catalyzed three-component deaminative coupling reaction of anilines, aldehydes and amines
  作者：Aldiyar Shakenov、Krishna Prasad Gnyawali、Chae S. Yi

  DOI：10.1039/d3ob00348e

  日期：——

  was found to be a highly effective catalyst for the three-component deaminative coupling reaction of anilines with aldehydes and allylamines to form 2,3-disubstituted quinoline products. The analogous coupling reaction of anilines with aldehydes and cyclic enamines led to the selective formation of the tricyclic quinoline derivatives. The reaction profile study showed that the imine is initially formed

  Ru–H 络合物 (PCy 3 ) 2 (CO)RuHCl ( 1) 被发现是苯胺与醛和烯丙胺的三组分脱氨偶联反应生成 2,3-二取代喹啉产物的高效催化剂。苯胺与醛和环烯胺的类似偶联反应导致选择性形成三环喹啉衍生物。反应曲线研究表明，亚胺最初是由苯胺和醛脱水偶联而成，然后与胺底物发生脱氨偶联和环化反应生成喹啉产物。催化偶联法提供了一种高效的 2,3-二取代喹啉衍生物合成方法，无需使用任何反应试剂或形成无用的副产物。
• PHARMACEUTICAL COMPOSITION CONTAINING FUSED HETERO-RING DERIVATIVE
  申请人：Tachibana Yuuki

  公开号：US20120277238A1

  公开（公告）日：2012-11-01

  The present invention provides a compound which indicates a histamine H4 receptor modulating activity. A compound represented by a formula (I): wherein A ring is a ring represented by the following formula: wherein R 1 is substituted or unsubstituted alkyl, etc., W is —O—, etc., n is an integer of 0 to 6; X is —N(R 7 )— or —O—; R 7 is hydrogen, substituted or unsubstituted alkyl, etc.; Y is —C(R 8 )═ or —N═; R 8 is hydrogen, substituted or unsubstituted alkyl, etc.; Z is ═O, ═S, etc.; B ring is a ring represented by the following formula: wherein R 10 is each independently substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted alkyloxy, substituted or unsubstituted amino; R 11 , R 12a and R 12b are each independently hydrogen or substituted or unsubstituted alkyl, etc.; p is an integer of 0 to 4, or its pharmaceutically acceptable salt, or a solvate thereof.
• 1,1-Dioxo-5,6-dihydro-[4,1,2]oxathiazines, a novel class of 11ß-HSD1 inhibitors for the treatment of diabetes
  作者：Thomas Böhme、Christian K. Engel、Géraldine Farjot、Stefan Güssregen、Torsten Haack、Georg Tschank、Kurt Ritter

  DOI：10.1016/j.bmcl.2013.05.102

  日期：2013.8

  Racemic cis-1,1-dioxo-5,6-dihydro-[4,1,2]oxathiazine derivative 4a was isolated as an impurity in a sample of a hit from a HTS campaign on 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). After separation by chiral chromatography the 4a-S, 8a-R enantiomer of compound 4a was identified as the true, potent enzyme inhibitor. The cocrystal structure of 4a with human and murine 11 beta-HSD1 revealed the unique binding mode of the oxathiazine series. SAR elucidation and optimization in regard to metabolic stability led to monocyclic tetramethyloxathiazines as exemplified by compound 21g. (C) 2013 Elsevier Ltd. All rights reserved.