(+)-(1R,2R)-trans-1,2,3,4-tetrahydro-1-(methylamino)2-naphthalenol | 169106-10-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+)-(1R,2R)-trans-1,2,3,4-tetrahydro-1-(methylamino)2-naphthalenol
• 英文别名: trans-1-Methylamino-2-hydroxy-tetralin；(1R,2R)-1-(methylamino)-1,2,3,4-tetrahydronaphthalen-2-ol
• CAS: 169106-10-9
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: KUDUKVRCFKJXBL-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-(1R,2R)-trans-1,2,3,4-tetrahydro-1-(methylamino)2-naphthalenol 在 正丁基锂 、 1,10-菲罗啉 、 potassium carbonate 作用下， 以 正己烷 为溶剂， 反应 1.33h， 生成 (1aS,7bR)-1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydronaphtho[1,2-b]azirin-1-ium
  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：

  1,2,3,4-四氢萘 在 水 、 溴 、 碳酸氢钠 、 potassium carbonate 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 24.0h， 生成 (+)-(1R,2R)-trans-1,2,3,4-tetrahydro-1-(methylamino)2-naphthalenol
  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

• Process for synthesis of D1 receptor antagonists
  申请人：Schering Corporation

  公开号：US20030199690A1

  公开（公告）日：2003-10-23

  In one embodiment, the present invention describes the synthesis of a compound of formula 1 and intermediates therefor.

  在一种实施方式中，本发明描述了化合物formula1的合成及其中间体。