(3RS)-7-chloro-1,3-dihydro-3-[(1SR)-1-hydroxypropyl]-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (3RS)-7-chloro-1,3-dihydro-3-[(1SR)-1-hydroxypropyl]-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one
• 英文别名: 7-chloro-3-(1-hydroxypropyl)-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one
• 化学式: C₁₉H₁₉ClN₂O₂
• 分子量: 342.825
• InChiKey: UMGRZAFSJZHDFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  去甲西泮 在 sodium methylate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 0.5h， 生成 (3RS)-7-chloro-1,3-dihydro-3-[(1SR)-1-hydroxypropyl]-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  摘要：

  The aldol reaction of the C(3) carbanion of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (2) with a series of aromatic and aliphatic aldehydes at -78 degrees afforded threolerythro diastereoisomers 3-16 of 7-chloro-1,3-dihydro-3-(hydroxymethyl)-1-methyl-5-phenyl-2H-1,4-benzodiazepinones, substituted at the C(3) side chain, in a ratio from 55:45 to 94:6 (Scheme 1). Lewis acids exhibited limited effect on the syn/ anti diastereoselectivity of this reaction, and kinetic control of the reaction was confirmed. H-1-NMR Data suggested the assignment of the threo relative configuration to the first-eluted diastereoisomers 3, 5, 7,and 9 on reversed-phase HPLC, and the erythro configuration to the second-eluted counterparts 4, 6, 8, and 10, respectively. The structures and relative configurations three and erythro of the diastereoisomers 5 and 6, respectively, were established by single-crystal X-ray analysis, confirming the assignment based on the H-1-NMR data. A tentative mechanistic explanation of the diastereoselectivity invokes the enolate anion of 1,3-dihydro-2H-1,4-benzodiazepin-2-one as the reactive species (Scheme 2). Acid-catalyzed hydrolytic ring opening of 3 afforded threo-beta-hydroxy-phenylalanine 17, whereas from 4, the N-(benzyloxy)carbonyl derivative 18 of erythro-beta-hydroxy-phenylalanine was obtained (Scheme 3); in both cases, neither elimination of H2O from the C(3)-CHOH moiety nor epimerization at C(3) were observed. This result opens a new pathway to various configurationally uniform alpha-amino-beta-hydroxy carboxylic acids and their congeners of biological importance.

  DOI：

  10.1002/(sici)1522-2675(20000315)83:3<603::aid-hlca603>3.0.co;2-1

文献信息

• ——
  作者：Dean Marković、Zdenko Hameršak、Aleksandar Višnjevac、Biserka Kojić-Prodić、Vitomir Šunjić

  DOI：10.1002/(sici)1522-2675(20000315)83:3<603::aid-hlca603>3.0.co;2-1

  日期：2000.3.15

  The aldol reaction of the C(3) carbanion of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (2) with a series of aromatic and aliphatic aldehydes at -78 degrees afforded threolerythro diastereoisomers 3-16 of 7-chloro-1,3-dihydro-3-(hydroxymethyl)-1-methyl-5-phenyl-2H-1,4-benzodiazepinones, substituted at the C(3) side chain, in a ratio from 55:45 to 94:6 (Scheme 1). Lewis acids exhibited limited effect on the syn/ anti diastereoselectivity of this reaction, and kinetic control of the reaction was confirmed. H-1-NMR Data suggested the assignment of the threo relative configuration to the first-eluted diastereoisomers 3, 5, 7,and 9 on reversed-phase HPLC, and the erythro configuration to the second-eluted counterparts 4, 6, 8, and 10, respectively. The structures and relative configurations three and erythro of the diastereoisomers 5 and 6, respectively, were established by single-crystal X-ray analysis, confirming the assignment based on the H-1-NMR data. A tentative mechanistic explanation of the diastereoselectivity invokes the enolate anion of 1,3-dihydro-2H-1,4-benzodiazepin-2-one as the reactive species (Scheme 2). Acid-catalyzed hydrolytic ring opening of 3 afforded threo-beta-hydroxy-phenylalanine 17, whereas from 4, the N-(benzyloxy)carbonyl derivative 18 of erythro-beta-hydroxy-phenylalanine was obtained (Scheme 3); in both cases, neither elimination of H2O from the C(3)-CHOH moiety nor epimerization at C(3) were observed. This result opens a new pathway to various configurationally uniform alpha-amino-beta-hydroxy carboxylic acids and their congeners of biological importance.