(R)-1-phenylbutan-1-amine hydrochloride

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R)-1-phenylbutan-1-amine hydrochloride
• 英文别名: (1R)-1-phenylbutan-1-amine hydrochloride；(R)-1-phenylbutylamine hydrochloride；(R)-1-PHENYLBUTYLAMINE-HCl；(1R)-1-phenylbutan-1-amine;hydrochloride
• 化学式: C₁₀H₁₅N*ClH
• 分子量: 185.697
• InChiKey: SRLJBKBDJRRHGL-HNCPQSOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.91
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-1-phenylbutan-1-amine hydrochloride 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.25h， 生成 (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-N-[(1R)-1-phenylbutyl]piperidine-3-carboxamide
  参考文献：
  名称：

  Synthesis and optimization of novel (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors

  摘要：

  We report synthesis and optimization of a series of (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of P-1', P-2' and P-3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.057
• 作为产物：
  描述：

  (S)-(-)-1-苯基-1-丁醇 在 盐酸 、 palladium 10% on activated carbon 、 二苯基膦叠氮化物 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 乙醇 、 乙酸乙酯 、 甲苯 为溶剂， 反应 51.0h， 生成 (R)-1-phenylbutan-1-amine hydrochloride
  参考文献：
  名称：

  Synthesis and optimization of novel (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors

  摘要：

  We report synthesis and optimization of a series of (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of P-1', P-2' and P-3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.057

文献信息

• Reversal Diastereoselectivity Between the Organomagnesium and Organolithium Reagents on Chiral <i>N</i>-<i>Tert</i>-Butylsulfinylaldimines for the Preparation of Chiral Amines
  作者：Chinnapillai Rajendiran、Periyandi Nagarajan、A. Naidu、P. K. Dubey

  DOI：10.1080/00397911.2014.909487

  日期：2014.10.18

  Abstract The asymmetric synthesis of both the enantiomer of chiral amines from the single chiral source of N-tert-butylsulfinylaldimines (3) by simply changing the organometallic reagents through diastereoselective addition. An efficient enantioselective synthesis of chiral amines including (S)-3-methyl-1-(2-piperidin-1-yl-phenyl)butyl amine (6a), a key intermediate to prepare antidiabetic drug repaglinide

  摘要 通过非对映选择性加成简单地改变有机金属试剂，从 N-叔丁基亚磺酰基醛亚胺 (3) 的单一手性来源不对称合成两种手性胺的对映异构体。报告了一种有效的对映选择性合成手性胺，包括 (S)-3-甲基-1-(2-哌啶-1-基-苯基) 丁胺 (6a)，这是制备抗糖尿病药物瑞格列奈 (1) 的关键中间体。图形概要
• One-Pot Synthesis of Chiral Nonracemic Amines
  作者：Caroline Roe、Heather Hobbs、Robert A. Stockman

  DOI：10.1021/jo201849j

  日期：2011.11.18

  One-pot five-component reactions of oxathiazolidine-S-oxides with mesitylmagnesium bromide, lithium bis(trimethylsilyl)amide, aldehydes and Grignard reagents afford chiral nonracemic amines or sulfinamides in good yields and high stereoselectivities.

  氧杂噻唑烷-S-氧化物与间苯二甲酸溴化镁，双（三甲基甲硅烷基）酰胺锂，醛和格氏试剂的一锅五组分反应可提供高收率和高立体选择性的手性非外消旋胺或亚磺酰胺。
• Asymmetric Reductive Amination: Convenient Access to Enantioenriched Alkyl-Alkyl or Aryl-Alkyl Substituted α-Chiral Primary Amines
  作者：Thomas C. Nugent、Abhijit K. Ghosh、Vijay N. Wakchaure、Rashmi R. Mohanty

  DOI：10.1002/adsc.200606073

  日期：2006.7

  step one is the hydrogenation (4–8 bar) of a prochiral ketone substrate in the presence of α-MBA, a Lewis acid [Ti(O-i-Pr)4, B(O-i-Pr)3, Al(O-i-Pr)3, or Zr(O-i-Pr)4], and a heterogeneous hydrogenation catalyst (Raney-Ni, Pt-C, Pd-C, Ru-C, or Rh-C), providing the amine diastereomers 2 in good to excellent yield and diastereoselectivity. Depending on the ketone examined (acyclic vs. cyclic, alkyl alkyl

  已经开发了用于生产旋光性高价值伯胺的两步法。第一步也是关键步骤是将前手性烷基烷基（非环状或环状）或芳基烷基（非环状或环状）酮与（R）-或（S）-α-甲基苄胺（α-MBA）进行不对称还原胺化。通过在第一步中同时在酮的前羰基碳上同时加入辅助剂和新的立体异构中心，可以避免手性辅助剂方法通常分步过度的过程。具体来说，第一步是在α-MBA，路易斯酸[Ti（O- i- Pr）4，B（O- i- Pr）3，铝（O- i-PR）3，或Zr（O-异PR）4 ]和多相氢化催化剂（阮内镍，铂-C，钯-碳，钌-C，或Rh-C），提供非对映体胺2在优良至优异的产率和非对映选择性。取决于酮已审查（无环对环状的，烷基烷基与芳基烷基，空间位阻对支配），非均相氢化催化剂，溶剂，和温度的正确组合是用于允许高产率和关键德具有实际的反应时间（通常为6-20小时）。在不存在所指出的路易斯酸之一的情况下进行反应导致形成大量的醇副产物（＞
• Synthesis and optimization of novel (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors
  作者：Yutaka Mori、Yasuyuki Ogawa、Akiyoshi Mochizuki、Yuji Nakamura、Teppei Fujimoto、Chie Sugita、Shojiro Miyazaki、Kazuhiko Tamaki、Takahiro Nagayama、Yoko Nagai、Shin-ichi Inoue、Katsuyoshi Chiba、Takahide Nishi

  DOI：10.1016/j.bmc.2013.06.057

  日期：2013.9

  We report synthesis and optimization of a series of (3S,5R)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of P-1', P-2' and P-3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys. (C) 2013 Elsevier Ltd. All rights reserved.