2-(甲基氨基)-5-氯二苯甲酮亚胺 | 5606-40-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(甲基氨基)-5-氯二苯甲酮亚胺
• 中文别名: 3-乙基-4-羰基-3,4-二氢咪唑并[5,1-d][1,2,3,5]四嗪-8-甲酰胺
• 英文名称: (2-methylamino-5-chlorophenyl)-phenyl-methane-imine
• 英文别名: 5-Chloro-2-(methylamino)benzophenone Imine；2-methylamino-5-chlorobenzophenone imine；2-(Methylamino)-5-chlorobenzophenone imine；2-(benzenecarboximidoyl)-4-chloro-N-methylaniline
• CAS: 5606-40-6
• 化学式: C₁₄H₁₃ClN₂
• 分子量: 244.724
• InChiKey: YIBUYDHSWMGPBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  35.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  氯(氟)乙酰氯 、 2-(甲基氨基)-5-氯二苯甲酮亚胺 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-氟-1,3-二氢-1-甲基-7-氯-5-苯基-2H-1,4-苯并二氮杂-2-酮
  参考文献：
  名称：

  Hydroxyquinazolines and their use as intermediates for pharmaceutical

  摘要：

  6-取代-2-卤代氟甲基-1,2-二氢-2-羟基-1-甲基-4-苯基喹唑啉及其在制备3-氟苯二氮䓬啉中的用途，后者可用作镇静剂、肌肉松弛剂和镇静剂。

  公开号：

  US04141895A1
• 作为产物：
  描述：

  N-(2-苯甲酰基-4-氯苯基)甲酰胺 在 氯化锌 氨 作用下， 以 N-甲基乙酰胺 、 甲醇 、 水 、 mineral oil 为溶剂， 生成 2-(甲基氨基)-5-氯二苯甲酮亚胺
  参考文献：
  名称：

  Hydroxyquinazolines and their use as intermediates for pharmaceutical

  摘要：

  6-取代-2-卤代氟甲基-1,2-二氢-2-羟基-1-甲基-4-苯基喹唑啉及其在制备3-氟苯二氮䓬啉中的用途，后者可用作镇静剂、肌肉松弛剂和镇静剂。

  公开号：

  US04141895A1

文献信息

• Synthetic studies on quinazoline derivatives. II. The reactions of 2-trichloro- and 2-trifluoroacetamidobenzophenones with primary amines.
  作者：MICHIHIRO YAMAMOTO、HISAO YAMAMOTO

  DOI：10.1248/cpb.29.2135

  日期：——

  The reaction of 5-chloro-2-trichloroacetamidobenzophenone (2a) with several primary alkylamines in DMSO gave high yields of 3-substituted 6-chloro-3, 4-dihydro-4-phenyl-4-trichloromethyl-2(1H)-quinazolinones 6, which were found to be formed by base-catalyzed and/or thermal cyclization and simultaneous rearrangement of the isomeric 5-chloro-2-trichloroacetamidobenzophenone alkylimines 5. Both compounds 5 and 6 were obtained when the reaction was effected in benzene. Treatment of the compound 2a with bulky amines such as isopropylamine and cyclohexylamine gave, under similar conditions, the corresponding benzophenone imines 5d and 5e exclusively, and these could be transformed into the quinazolinones 6d and 6e, respectively, on heating in pyridine or HMPT. The reaction of N-substituted trichloroacetamidobenzophenones 2m and 3n with N-(2-aminoethyl) morpholine as well as ammonia in DMSO yielded the 1-alkylaminobenzophenone imines 4m-o, which on treatment with trichloroacetyl chloride were readily cyclized to give the corresponding 1-substituted 4-trichloromethylquinazolinones 6m-o. The trichloromethyl group of the 1-unsubstituted quinazolinones 6 was easily displaced by a nucleophile such as hydride, alkoxide or hydroxide under base catalysis to give the 3, 4-dihydro-2 (1H)-quinazolinone derivative 9, 10 or 11 almost quantitatively, whereas the 1, 3-disubstituted quinazolinone 6o was not affected. The sodium borohydride reduction of the methylimine 5a at room temperature mainly afforded the trichloroacetamidobenzhydrylamine 8a, which underwent thermal cyclization to the quinazolinone 9a via split of chloroform. In contrast, the reaction of 5-chloro-2-trifluoroacetamidobenzophenone (2p) with some primary alkylamines in DMSO produced the trifluoroacetamidobenzophenone alkylimines 5p-r, which on treatment with sodium borohydride could be converted only to 3-substituted 6-chloro-3, 4-dihydro-4-phenyl-2-trifluoromethylquinazolines 15. These procedures were successfully utilized in syntheses of the imidazo [1, 2-c] quinazolinone 16, oxazolo [3, 2-c] quinazolinones 17t and 17v, and 1, 3-oxazino [3, 2-c] quinazolinone 17u.

  5-氯-2-三氯乙酰氨基苯并酮(2a)与几种初级烷基胺在DMSO中反应，得到了高产率的3取代的6-氯-3, 4-二氢-4-苯基-4-三氯甲基-2(1H)-喹唑啉酮 6，这些化合物被发现是通过碱催化和/或热环化以及异构体5-氯-2-三氯乙酰氨基苯并酮烷基亚胺的同时重排形成的。两种化合物5和6在苯中反应时均可获得。用体积较大的胺如异丙胺和环己胺处理化合物2a，在类似条件下，得到了相应的苯并酮亚胺5d和5e，经过加热于吡啶或HMPT中，这些亚胺分别可以转化为喹唑啉酮6d和6e。N-取代的三氯乙酰氨基苯并酮2m和3n与N-(2-氨基乙基)吗啉和氨在DMSO中反应，生成了1-烷基氨基苯并酮亚胺4m-o，经过与三氯乙酸酰氯的处理后，这些亚胺可以被迅速环化，得到相应的1-取代的4-三氯甲基喹唑啉酮6m-o。1-未取代的喹唑啉酮6中的三氯甲基基团在碱催化下可以很容易地被氢负离子、烷氧基或氢氧根等亲核试剂取代，几乎定量地产生3, 4-二氢-2(1H)-喹唑啉酮衍生物9、10或11，而1, 3-二取代的喹唑啉酮6o则没有受到影响。在室温下，甲基亚胺5a的钠硼氢化物还原主要产生了三氯乙酰氨基苯基胺8a，该物质经过热环化通过氯仿分解生成喹唑啉酮9a。相比之下，5-氯-2-三氟乙酰氨基苯并酮(2p)与一些初级烷基胺在DMSO中反应，生成了三氟乙酰氨基苯并酮烷基亚胺5p-r，经过与钠硼氢化物的处理后，仅能转化为3取代的6-氯-3, 4-二氢-4-苯基-2-三氟甲基喹唑啉15。这些程序成功应用于合成咪唑[1, 2-c]喹唑啉酮16、噁唑[3, 2-c]喹唑啉酮17t和17v，以及1, 3-噁唑啉[3, 2-c]喹唑啉酮17u。
• Mechanism of Alkaline Hydrolysis of Diazepam
  作者：Shen K. Yang

  DOI：10.1002/jccs.199800044

  日期：1998.4

  AbstractDiazepam (1) is a frequently prescribed hypnotic/anxiolytic drug in worldwide use. Compound 1 is hydrolyzed in alkaline medium to form 2‐methylamino‐5‐chlorobenzophenone imine (2) and 2‐methylamino‐5‐chlorobenzophenone (3); the ratio of 2:3 increases with increasing NaOH concentration (J. Pharm. Sci. 85, 745–748, 1996). The mechanism in the conversion of 1 to 2 and 3 via various intermediates is the subject of this report. Results of hydrolysis kinetics and structural identification of some intermediate products indicated an initial hydroxide attack at the C2‐carbonyl carbon of 1, resulting in the formation of a dioxide (7, 7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2,2‐dioxide). Compound 7 was characterized by proton NMR spectroscopy and via its monomethyl ether (8, 7‐chloro‐1,3‐dihydro‐2‐hydroxy‐2‐methoxy‐l‐methyl‐5‐pheny]‐2H‐1,4‐benzodiazepine). The seven‐member diazepine ring of 7 opened at the N1‐C2 bond to form a glycinate [5, 2‐methylamino‐5‐chloro‐α‐(phenylhenzylidene)glycinate]. Compound 7 (and/or 5) underwent an additional hydroxide attack at the C5‐N4 imine bond to form a tetrahedral intermediate, which decomposed to form 2 and 3.
• A New Approach to the 1,4-Benzodiazepine Ring System
  作者：Paola Giacconi、Elisabetta Rossi、Riccardo Stradi、Rosanna Eccel

  DOI：10.1055/s-1982-29948

  日期：——
• YAMAMOTO, MICHIHIRO;YAMAMOTO, HISAO, CHEM. AND PHARM. BULL., 1981, 29, N 8, 2135-2156
  作者：YAMAMOTO, MICHIHIRO、YAMAMOTO, HISAO

  DOI：——

  日期：——
• GIACCONI, P.;ROSSI, E.;STRADI, R.;ECCEL, R., SYNTHESIS, BRD, 1982, N 9, 789-791
  作者：GIACCONI, P.、ROSSI, E.、STRADI, R.、ECCEL, R.

  DOI：——

  日期：——