sec-Butyl-(5,6-dimethoxy-indan-2-yl)-amine | 390361-09-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: sec-Butyl-(5,6-dimethoxy-indan-2-yl)-amine
• 英文别名: N-butan-2-yl-5,6-dimethoxy-2,3-dihydro-1H-inden-2-amine
• CAS: 390361-09-8
• 化学式: C₁₅H₂₃NO₂
• 分子量: 249.353
• InChiKey: QSJGCFORWQNPTK-UHFFFAOYSA-N

物化性质

• 熔点：
  256-258 °C
• 沸点：
  356.8±42.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丙醛 、 sec-Butyl-(5,6-dimethoxy-indan-2-yl)-amine 在 sodium triacetoxyborohydride 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 以70%的产率得到sec-Butyl-(5,6-dimethoxy-indan-2-yl)-propyl-amine
  参考文献：
  名称：

  Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-N-alkyl- and N-Alkylaryl-Substituted 2-Aminoindans

  摘要：

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.

  DOI：

  10.1021/jm010145w
• 作为产物：
  描述：

  3-(3,4-dimethoxy-phenyl)-propionyl chloride 在 10percent Pd/C 盐酸 、 三氯化铝 、 亚硝酸丁酯 、 硫酸 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 20.0~40.0 ℃ 、344.75 kPa 条件下， 反应 30.5h， 生成 sec-Butyl-(5,6-dimethoxy-indan-2-yl)-amine
  参考文献：
  名称：

  Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-N-alkyl- and N-Alkylaryl-Substituted 2-Aminoindans

  摘要：

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.

  DOI：

  10.1021/jm010145w

文献信息

• Dopamine D₃ Receptor Antagonists. 1. Synthesis and Structure−Activity Relationships of 5,6-Dimethoxy-<i>N</i>-alkyl- and <i>N</i>-Alkylaryl-Substituted 2-Aminoindans
  作者：Susanne R. Haadsma-Svensson、Kerry A. Cleek、Dac M. Dinh、J. Neil Duncan、Christopher L. Haber、Rita M. Huff、Mary E. Lajiness、Nanette F. Nichols、Martin W. Smith、Kjell A. Svensson、Matt J. Zaya、Arvid Carlsson、Chiu-Hong Lin

  DOI：10.1021/jm010145w

  日期：2001.12.1

  5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D-3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D-3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D-3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D-3 binding affinity, the D-2 affinity is also enhanced, resulting in a less than 4-fold preference for the D-3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D-3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3. Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (similar to 65%) from the indanone 5c.