4-phenyl-3-piperidinomethyl-3,4-dihydro-2H-isoquinolin-1-one | 112972-13-1

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 4-phenyl-3-piperidinomethyl-3,4-dihydro-2H-isoquinolin-1-one
• 英文别名: 4-phenyl-3-piperidinomethyl-3,4-dihydro-2H-isoquinolin-1-one；4-Phenyl-3-piperidinomethyl-3,4-dihydro-2H-isochinolin-1-on
• CAS: 112972-13-1
• 化学式: C₂₁H₂₄N₂O
• 分子量: 320.434
• InChiKey: MBGVQDSCDDYSKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  32.34
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  3-phenyl-2-piperidinomethyl-indan-1-one; hydrochloride 在 sodium azide 、 硫酸 作用下， 生成 4-phenyl-3-piperidinomethyl-3,4-dihydro-2H-isoquinolin-1-one
  参考文献：
  名称：

  施密特反应中的立体和静电效应

  摘要：

  已经通过施密特反应从环酮合成了几种基本取代的内酰胺。

  DOI：

  10.1002/hlca.19560390234

文献信息

• Azacarbocycles and process for their manufacture
  申请人：CIBA PHARM PROD INC

  公开号：US02785159A1

  公开（公告）日：1957-03-12

  The invention comprises heterocyclic compounds with 6 or 7 atoms in the heterocyclic ring, an oxo group ortho to a ring-nitrogen atom and a tertiary amino-alkyl substituent ortho to the nitrogen atom on the other side. These are made by treating with hydrazoic acid the corresponding 5- or 6-membered carbocyclic ring compounds whereby -NH- is inserted in the ring. The hydrazoic acid may be formed in situ from an azide such as sodium azide in the presence of highly concentrated sulphuric acid. Alternatively the hydrazoic acid may be added as a solution in an organic solvent. The products form salts with acids such as hydrohalic, sulphuric, nitric, phosphoric, thiocyanic, acetic, propionic, oxalic, malonic, succinic, malic, isethionic and other sulphonic acids; they may also be quaternated with higher alkyl derivatives such as dodecyl chloride. Examples show the preparation of the following: (1) 3-piperidinomethyl - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline and hydrochloride from 2-piperidinomethyl - indan - 1 - one; (2) 2 - piperidinomethyl - 7 - oxo - 1:2:3:4 - tetrahydro - 5:6-benzazepine and hydrochloride from 2-piperidinomethyl - 1 - tetralone; (3) 3 - (b - piperidinoethyl) - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline from 2-(b -piperidinoethyl)-indan-1-one; (4) 2 - (b - piperidinoethyl) - 7 - oxo-1:2:3:4 - tetrahydro - 5:6 - benzazepine from 2 - (b - piperidinoethyl) - 1 - tetralone; (5) 3-diethylaminomethyl - 1 - oxo - 1:2:3:4-tetrahydroisoquinoline from 2-diethylaminomethyl - indan - 1 - one; the dimethylaminomethyl compound is made similarly; (6) 2-piperidinomethyl - 7 - oxo - azepidine and hydrochloride from 2 - piperidinomethylcyclohexanone; (7) 3 - (b - piperidinoethyl)-6:7 - dimethoxy - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline from 2 - (b - piperidinoethyl) - 5:6 - dimethoxy - indan - 1 - one; (8) 3 - piperidinomethyl - 4 - phenyl - 1 - oxo-1:2:3:4 - tetrahydro - isoquinoline from 2-piperidinomethyl - 3 - phenyl - indan - 1 - one; (9) 2 - piperidinomethyl - 4 - phenyl - 7 - oxo-1:2:3:4 - tetrahydro - 5:6 - benzazepine from 2 - piperidinomethyl - 4 - phenyl - 1 - tetralone; (10) 3 - (b - dimethylamino - propyl) - 6:7 - dimethoxy - 1 - oxo - 1:2:3:4 - tetrahydro - isoquinoline from 2 - (b - dimethylamino - propyl)-5:6-dimethoxy-indan-1-one. 2 - Piperidinomethyl - 3 - phenyl - indan - 1-one and 2 - piperidinomethyl - 4 - phenyl - 1-tetralone are obtained as hydrochlorides by condensing piperidine and paraformaldehyde with 3 - phenyl - indan - 1 - one and 4 - phenyl - 1-tetralone respectively. 2 - (b - Piperidinoethyl) - indan - 1 - one, 2-(b - piperidinoethyl) - 5:6 - dimethoxy - indan - 1-one and 2 - (b - dimethylaminopropyl) - 5:6 - dimethoxy - indan - 1 - one are made by ring closure of diethyl benzyl - (b - piperidinoethyl)-malonate, diethyl 3:4 - dimethoxybenzyl - (b - piperidinoethyl) - malonate and diethyl 3 : 4 - dimethoxybenzyl - (b - dimethylaminopropyl)-malonate respectively. The third product is obtained as hydrochloride. 2 - (b - Piperidinoethyl) - 1 - tetralone is obtained by condensing N-(b -chloroethyl)-piperidine with di-(tetrahydropyranyl) b -phenethylmalonate and ring closing the product.

  该发明涉及具有6或7个原子的杂环化合物，其中杂环环上的一个氧基与另一侧的氮原子正交，并且具有一个三级氨基烷基取代物。这些化合物通过用叠氮酸处理相应的5或6元环碳环化合物制备而成，从而在环中插入-NH-。叠氮酸可以在高浓硫酸存在下从偶氮化物（如偶氮酸钠）中形成。或者，叠氮酸可以作为有机溶剂中的溶液添加。这些产物与酸（如氢卤酸、硫酸、硝酸、磷酸、硫氰酸、乙酸、丙酸、草酸、马来酸、琥珀酸、苹果酸、异乙烯磺酸和其他磺酸）形成盐，并且可以用高级烷基衍生物（如十二烷基氯）进行季铵化。实例显示了以下化合物的制备：（1）从2-哌啶甲基-茚-1-酮制备3-哌啶甲基-1-氧代-1：2：3：4-四氢-异喹啉及其盐酸盐；（2）从2-哌啶甲基-1-四氢萘酮制备2-哌啶甲基-7-氧代-1：2：3：4-四氢-5：6-苯并环庚烷及其盐酸盐；（3）从2-(b-哌啶乙基)-茚-1-酮制备3-(b-哌啶乙基)-1-氧代-1：2：3：4-四氢-异喹啉；（4）从2-(b-哌啶乙基)-1-四氢萘酮制备2-(b-哌啶乙基)-7-氧代-1：2：3：4-四氢-5：6-苯并环庚烷；（5）从2-二乙氨甲基-茚-1-酮制备3-二乙氨甲基-1-氧代-1：2：3：4-四氢-异喹啉；类似地制备了二甲氨基甲基化合物；（6）从2-哌啶甲基环己酮制备2-哌啶甲基-7-氧代-氮杂环庚烷及其盐酸盐；（7）从2-(b-哌啶乙基)-5：6-二甲氧基-茚-1-酮制备3-(b-哌啶乙基)-6：7-二甲氧基-1-氧代-1：2：3：4-四氢-异喹啉；（8）从2-哌啶甲基-3-苯基-茚-1-酮制备3-哌啶甲基-4-苯基-1-氧代-1：2：3：4-四氢-异喹啉；（9）从2-哌啶甲基-4-苯基-1-四氢萘酮制备2-哌啶甲基-4-苯基-7-氧代-1：2：3：4-四氢-5：6-苯并环庚烷；（10）从2-(b-二甲氨基丙基)-5：6-二甲氧基-茚-1-酮制备3-(b-二甲氨基丙基)-6：7-二甲氧基-1-氧代-1：2：3：4-四氢-异喹啉。2-哌啶甲基-3-苯基茚-1-酮和2-哌啶甲基-4-苯基-1-四氢萘酮分别与哌啶和多聚甲醛缩合，得到盐酸盐。2-(b-哌啶乙基)-茚-1-酮、2-(b-哌啶乙基)-5：6-二甲氧基-茚-1-酮和2-(b-二甲氨基丙基)-5：6-二甲氧基-茚-1-酮通过闭环得到，闭环前杂环上的二乙氨基苯甲酸二乙酯、二乙氨基苯甲酸二乙酯和二甲基氨基丙基苯甲酸二乙酯。第三个产物以盐酸盐的形式得到。2-(b-哌啶乙基)-1-四氢萘酮通过N-(b-氯乙基)-哌啶和双-(四氢吡喃基)-b-苯乙酸酯缩合并环合得到。