(RS)-5-(4-chlorophenyl)-2-piperidone | 41216-03-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (RS)-5-(4-chlorophenyl)-2-piperidone
• 英文别名: 5-(4-chlorophenyl)piperidin-2-one；5-(p-Chlorphenyl)-2-piperidon；2-Piperidinone, 5-(4-chlorophenyl)-
• CAS: 41216-03-9
• 化学式: C₁₁H₁₂ClNO
• 分子量: 209.675
• InChiKey: PMIWQYDBCMPDAS-UHFFFAOYSA-N

物化性质

• 熔点：
  174 °C
• 沸点：
  399.9±42.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (RS)-5-(4-chlorophenyl)-2-piperidone 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 41.0h， 生成 7-(4-Chloro-phenyl)-2-oxo-3,4,6,7,8,9-hexahydro-2H-quinolizine-1-carboxylic acid methyl ester
  参考文献：
  名称：

  新型潜在抗精神病药的设计，合成和X射线数据。取代的7-苯基喹唑烷：立体特异性，抗精神病药和抗伤害感受性。

  摘要：

  选择半刚性7-苯基喹唑烷系统设计新的潜在抗精神病药是因为它满足了对多巴胺受体具有高亲和力所需的最小结构和空间要求的早期考虑，此外，还留下了许多变化的机会。仿照丁香酚结构建模的初始化合物5a实际上是无活性的，而在苯环上引入取代基和其他任选的结构元素可通过提供额外的结合力来改善多巴胺的拮抗性能。最初，获得了氯丙嗪效价范围内的化合物：（9aH）-2-叔丁基-7-（2,4-二氯苯基）八氢-2H-喹诺嗪-2-醇（5e）。通过5c的光学分辨率，已证明其生物活性存在于（-）对映异构体中。通过单晶X射线分析确定（-）-5e的绝对构型为2S，7R，9aR。可选结构元素的进一步变化导致出乎意料地发现了具有强抗伤害感受特性的化合物，例如（2R，7S，9aS）-2-丁基辛基-氢-7-苯基-2H-喹啉-2-乙酸丁酯[（+ ）-26]。有趣的是，该化合物属于与抗精神病药样（-）-5e相反的对映体系列。

  DOI：

  10.1021/jm00368a011
• 作为产物：
  描述：

  巴氯芬 在 盐酸 、 sodium hydroxide 、 三乙基硼氢化锂 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 132.5h， 生成 (RS)-5-(4-chlorophenyl)-2-piperidone
  参考文献：
  名称：

  Synthesis and Pharmacology of the Baclofen Homologues 5-Amino-4-(4-chlorophenyl)pentanoic Acid and the R- and S-Enantiomers of 5-Amino-3-(4-chlorophenyl)pentanoic Acid

  摘要：

  (RS)-5-Amino-4-(4-chlorophenyl)pentanoic acid (10) and the R-form (11) and S-form (12) of (RS)-5-amino-3-(4-chlorophenyl)pentanoic acid, which are homologues of the 4-aminobutanoic acid(B) (GABA(B)) receptor agonist (RS)-4-amino-3-(4-chlorophenyl)butanoic acid (baclofen), were synthesized. Compound 10 was synthesized by homologation at the carboxyl end of baclofen using a seven-step reaction sequence. N-Boc-protected (4R,5R)-4-(4-chlorophenyl)-5-hydroxy-2-piperidone (18) was deoxygenated via a modified Barton-McCombie reaction to give N-Boc-protected (R)-4-(4-chlorophenyl)-2-piperidone (20), which was ring opened and deprotected to give 11.HCl. The corresponding S-enantiomer, 12.HCl, was synthesized analogously from the 4S,5S-enantiomer of 18, compound 21. The enantiomeric purities of 11.HCl (ee = 99.8%) and 12.HCl (ee = 99.3%) were determined by chiral HPLC. Compound 10 did not show detectable affinity for GABA(A) or GABA(B) receptor sites and was inactive as an agonist or an antagonist at GABA(B) receptors in the guinea pig ileum. Like the enantiomers of baclofen, neither 11 nor 12 showed detectable affinity for GABA(A) receptor sites, and in agreement with the findings far (S)-baclofen, 12 did not interact significantly with GABA(B) receptor sites. Compound 11 (IC50 = 7.4 +/- 0.6 mu M), a homologue of (R)-baclofen (2), was shown to be some 50 times weaker than 2 (IC50 = 0.14 +/- 0.01 mu M) as an inhibitor of GABA(B) binding. Accordingly, 11 (EC50 = 150 +/- 23 mu M) was shown to be weaker than 2 (EC50 = 11 +/- 1 mu M) as an inhibitor of electrically induced contractions of the guinea pig ileum. However, whereas this effect of 2 was sensitive to the GABA(B) antagonist, CGP35348 (4), the inhibition by 11 was not significantly affected. Furthermore, 12 (EC50 = 310 +/- 16 mu M) was shown to be one-half as potent as 11 in this test system, and this effect of 12 also was insensitive to 4. The dissimilarities of the pharmacological effects of 2 and compounds 11 and 12 were emphasized by the observation that whereas 2 only inhibits the ileum contraction by 59 +/- 5%, 11 as well as 12 were shown to inhibit this response by approximately 94%. Neither 11 nor 12 appeared to affect significantly cholinergic mechanisms in the ileum, and their mechanism(s) of action remain enigmatic.

  DOI：

  10.1021/jm990076+

文献信息

• Regioselective Reduction of N-Alkyl-3-sulfonyl Glutarimide. Formal Synthesis of 1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine and Homobaclofen
  作者：Shui-Tein Chen、Meng-Yang Chang

  DOI：10.3987/com-02-9626

  日期：——

  hydroxypiperidinones which werefurther dehydrated to two pyridin-2-ones in the presence of boron trifluoride etherate. Cycloaddition and regioselective reduction were combined to synthesize 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine and homobaclofen.

  N-烷基-3-磺酰基戊二酰亚胺用 (1) 氢化钠然后用氢化铝锂或 (2) 硼氢化钠还原产生两种不同类型的区域选择性还原的羟基哌啶酮，它们在三氟化硼醚合物。环加成和区域选择性还原相结合，合成了1,2,3,4,6,7,12,12b-八氢吲哚[2,3-a]喹啉和高巴氯芬。