(+/-)-(1RS)-1-(4-Chloro-3-methoxyphenyl)-3,4-dihydro-2(1H)-naphthalenone

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+/-)-(1RS)-1-(4-Chloro-3-methoxyphenyl)-3,4-dihydro-2(1H)-naphthalenone
• 英文别名: (1RS)-1-(4-Chloro-3-methoxyphenyl)-3,4-dihydro-2(1H)-naphthalenone；(+)-(1RS)-1-(4-chloro-3-methoxyphenyl)-3,4-dihydro-2(1H)-naphthalenone；1-(4-chloro-3-methoxyphenyl)-3,4-dihydro-1H-naphthalen-2-one
• 化学式: C₁₇H₁₅ClO₂
• 分子量: 286.758
• InChiKey: TWNKFWVTGQVYAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-(1RS)-1-(4-Chloro-3-methoxyphenyl)-3,4-dihydro-2(1H)-naphthalenone 在 甲酸 、 甲烷磺酸 、 二对甲苯酰基-L-酒石酸 、 borane tert-butylamine 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 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：

  4-(4-chloro-3-methoxyphenyl)-1,2-dihydronaphthalene 在 Oxone 、 对甲苯磺酸 作用下， 以 丙酮 、 甲苯 为溶剂， 生成 (+/-)-(1RS)-1-(4-Chloro-3-methoxyphenyl)-3,4-dihydro-2(1H)-naphthalenone
  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

• Preparation of alpha-(3,4-disubstituted aryl) cyclic ketones
  申请人：Schering Corporation

  公开号：US04992591A1

  公开（公告）日：1991-02-12

  A method for producing a compound of the formula ##STR1## wherein: R.sup.1, R.sup.11 and R.sup.12 may be the same or different and each is hydrogen or alkyl; Q is methylene, --O-- or --S--; m and n are independently variable and may each have a value of 0, 1 or 2; X is hydrogen, halo, alkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, hydroxy, alkoxy or trifluoromethyl; Y is hydrogen, hydroxy, alkoxy, ##STR2## --N(R.sup.1).sub.2, ##STR3## where R.sup.1 is as defined above; ring t represents a fused thiophene or fused benzene ring, said fused benzene ring optionally being substituted with a substituent Z as defined below; and Z is X as defined above, amino, alkylamino or ##STR4## wherein R.sup.10 is hydrogen, alkyl or aryl}, comprising reacting a compound of formula II or formula III ##STR5## with a compound of the formula where Hal is a halogen; and R.sup.13 is acetyl, or Si(R.sup.14).sub.3 where each R.sup.14 independently is alkyl or aryl is disclosed.

  一种生产化合物的方法，其化学式为##STR1##其中：R.sup.1，R.sup.11和R.sup.12可以相同也可以不同，每个都是氢或烷基；Q是亚甲基，-O-或-S-；m和n是独立可变的，每个可以取0、1或2的值；X是氢，卤素，烷基，烷硫基，烷基亚硫酰基，烷基磺酰基，羟基，烷氧基或三氟甲基；Y是氢，羟基，烷氧基，##STR2##-N(R.sup.1).sub.2，##STR3##其中R.sup.1如上定义；环t代表一个融合的噻吩环或融合的苯环，所述的融合的苯环可以选择性地用下面定义的取代基Z取代；Z是上述定义的X，氨基，烷基氨基或##STR4##其中R.sup.10是氢，烷基或芳基}，包括将化合物II或化合物III的化学式与化合物的化学式反应，其中Hal是卤素；R.sup.13是乙酰基，或Si(R.sup.14).sub.3，其中每个R.sup.14独立地是烷基或芳基。
• US4992591A
  申请人：——

  公开号：US4992591A

  公开（公告）日：1991-02-12
• 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.