(1RS,2SR)-1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,-7b-tetrahydro-1H-naphth[1,2-b]aziridinium tetrafluoroborate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (1RS,2SR)-1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,-7b-tetrahydro-1H-naphth[1,2-b]aziridinium tetrafluoroborate
• 英文别名: (1aS,7bR)-1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydronaphtho[1,2-b]azirin-1-ium;tetrafluoroborate
• 化学式: BF₄*C₁₅H₂₂NO₂
• 分子量: 335.15
• InChiKey: NULBKPZGKFVRMR-RDXSVFNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1RS,2SR)-1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,-7b-tetrahydro-1H-naphth[1,2-b]aziridinium tetrafluoroborate 在 甲烷磺酸 、 二对甲苯酰基-L-酒石酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 90.0h， 生成 依考匹泮
  参考文献：
  名称：

  Novel Stereoselective Syntheses of the Fused Benzazepine Dopamine D₁ Antagonist (6aS,13bR)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H- benzo[d]naphth[2,1-b]azepin-12-ol (Sch 39166):  1. Aziridinium Salt Based Syntheses

  摘要：

  Several novel enantioselective syntheses of the dopamine D-1 antagonist (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7- methyl-5H-benzo[d]naphth[2,1-b]azepin-12-ol (2) are described in which the key intermediate was 1-(2,2 dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydro-1H-naphth[1,2-b] aziridinium salt (20), The latter species was prepared either from 1-(2,2-dimethoxyethyl)-1a,2,3,7b-tetrahydro-]H-naphth[1,2-b]- azirine (18) by methylation or from the tertiary amino alcohols 1-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-2 -naphthalenol (23) or 2-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro -1-naphthalenol (24) by tosylation and in situ ring closure. Regioselective trapping of 20 with Grignard reagent (4-chloro-3-methoxyphenyl)magnesium bromide (10) then afforded the transamine 1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4 -tetrahydro-N-methyl-2-naphth-alenamine (22), which was cyclized to give 11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-12-methoxy-5H-benzo [d]- naphth[2,1-b]azepine (9), a known precursor of 2, Several enantioselective syntheses, including a Jacobsen epoxidation route, a de novo synthesis from L-homophenylalanine, and a classical salt resolution sequence, were developed for the preparation of the key intermediates in chiral form.

  DOI：

  10.1021/op970121s
• 作为产物：
  描述：

  1,2-二氢萘 在 potassium hydrogencarbonate 、 三乙胺 、 二溴三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 54.58h， 生成 (1RS,2SR)-1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,-7b-tetrahydro-1H-naphth[1,2-b]aziridinium tetrafluoroborate
  参考文献：
  名称：

  Novel Stereoselective Syntheses of the Fused Benzazepine Dopamine D₁ Antagonist (6aS,13bR)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H- benzo[d]naphth[2,1-b]azepin-12-ol (Sch 39166):  1. Aziridinium Salt Based Syntheses

  摘要：

  Several novel enantioselective syntheses of the dopamine D-1 antagonist (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7- methyl-5H-benzo[d]naphth[2,1-b]azepin-12-ol (2) are described in which the key intermediate was 1-(2,2 dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydro-1H-naphth[1,2-b] aziridinium salt (20), The latter species was prepared either from 1-(2,2-dimethoxyethyl)-1a,2,3,7b-tetrahydro-]H-naphth[1,2-b]- azirine (18) by methylation or from the tertiary amino alcohols 1-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-2 -naphthalenol (23) or 2-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro -1-naphthalenol (24) by tosylation and in situ ring closure. Regioselective trapping of 20 with Grignard reagent (4-chloro-3-methoxyphenyl)magnesium bromide (10) then afforded the transamine 1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4 -tetrahydro-N-methyl-2-naphth-alenamine (22), which was cyclized to give 11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-12-methoxy-5H-benzo [d]- naphth[2,1-b]azepine (9), a known precursor of 2, Several enantioselective syntheses, including a Jacobsen epoxidation route, a de novo synthesis from L-homophenylalanine, and a classical salt resolution sequence, were developed for the preparation of the key intermediates in chiral form.

  DOI：

  10.1021/op970121s

文献信息

• Novel Stereoselective Syntheses of the Fused Benzazepine Dopamine D₁ Antagonist (6a<i>S</i>,13b<i>R</i>)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5<i>H</i>- benzo[<i>d</i>]naphth[2,1-<i>b</i>]azepin-12-ol (Sch 39166):  1. Aziridinium Salt Based Syntheses
  作者：Richard W. Draper、Donald Hou、Radha Iyer、Gary M. Lee、Jimmy T. Liang、Janet L. Mas、Wanda Tormos、Eugene J. Vater、Frank Günter、Ingrid Mergelsberg、Dominik Scherer

  DOI：10.1021/op970121s

  日期：1998.5.1

  Several novel enantioselective syntheses of the dopamine D-1 antagonist (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7- methyl-5H-benzo[d]naphth[2,1-b]azepin-12-ol (2) are described in which the key intermediate was 1-(2,2 dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydro-1H-naphth[1,2-b] aziridinium salt (20), The latter species was prepared either from 1-(2,2-dimethoxyethyl)-1a,2,3,7b-tetrahydro-]H-naphth[1,2-b]- azirine (18) by methylation or from the tertiary amino alcohols 1-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-2 -naphthalenol (23) or 2-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro -1-naphthalenol (24) by tosylation and in situ ring closure. Regioselective trapping of 20 with Grignard reagent (4-chloro-3-methoxyphenyl)magnesium bromide (10) then afforded the transamine 1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4 -tetrahydro-N-methyl-2-naphth-alenamine (22), which was cyclized to give 11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-12-methoxy-5H-benzo [d]- naphth[2,1-b]azepine (9), a known precursor of 2, Several enantioselective syntheses, including a Jacobsen epoxidation route, a de novo synthesis from L-homophenylalanine, and a classical salt resolution sequence, were developed for the preparation of the key intermediates in chiral form.