(R)-7-amino-5-benzyl-7-methyl-5-azaspiro[2.4]heptane | 915302-85-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-7-amino-5-benzyl-7-methyl-5-azaspiro[2.4]heptane
• 英文别名: (+)-(7R)-7-amino-5-benzyl-7-methyl-5-azaspiro[2.4]heptane；(7R)-5-benzyl-7-methyl-5-azaspiro[2.4]heptan-7-amine
• CAS: 915302-85-1
• 化学式: C₁₄H₂₀N₂
• 分子量: 216.326
• InChiKey: ISCHGRWESPMROQ-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-7-amino-5-benzyl-7-methyl-5-azaspiro[2.4]heptane 在 palladium 10% on activated carbon 、 水 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 41.0h， 生成 (+)-7-[(R)-7-(tert-butoxycarbonylamino)-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluations of Novel 7-[7-Amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-8-methoxyquinolines with Potent Antibacterial Activity against Respiratory Pathogens

  摘要：

  Novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]- 8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 2a and 2b were designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Among these, compound 2a possessing (S)-configuration for the asymmetrical carbon on the pyrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens including Gram-positive (Streptococcus pneumoniae and Staphylococcus aureus), Gram-negative (Haemophilus influenzae and Moraxcella catarrhalis), and atypical strains (Chalmydia pneumoniae and Mycoplasma pneumoniae), as well as multidrug-resistant Streptococcus pneumoniae and quinolone-resistant and methicillin-resistant Staphylococcus aureus). Furthermore, compound 2a showed excellent in vivo activity against the experimental murine pneumonia model due to multidrug resistant Streptococcus pneumoniae (MDRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies.

  DOI：

  10.1021/jm301650g
• 作为产物：
  描述：

  1-(1-amino-1-cyanoethyl)-1-cyclopropanecarboxylic acid tert-butyl ester 在 盐酸 、 lithium aluminium tetrahydride 、 氢气 、 sodium hydride 、 六甲基二硅氮烷 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 、 mineral oil 为溶剂， 反应 22.34h， 生成 (R)-7-amino-5-benzyl-7-methyl-5-azaspiro[2.4]heptane
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluations of Novel 7-[7-Amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-8-methoxyquinolines with Potent Antibacterial Activity against Respiratory Pathogens

  摘要：

  Novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]- 8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 2a and 2b were designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Among these, compound 2a possessing (S)-configuration for the asymmetrical carbon on the pyrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens including Gram-positive (Streptococcus pneumoniae and Staphylococcus aureus), Gram-negative (Haemophilus influenzae and Moraxcella catarrhalis), and atypical strains (Chalmydia pneumoniae and Mycoplasma pneumoniae), as well as multidrug-resistant Streptococcus pneumoniae and quinolone-resistant and methicillin-resistant Staphylococcus aureus). Furthermore, compound 2a showed excellent in vivo activity against the experimental murine pneumonia model due to multidrug resistant Streptococcus pneumoniae (MDRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies.

  DOI：

  10.1021/jm301650g

文献信息

• METHOD FOR PRODUCING ASYMMETRIC TETRASUBSTITUTED CARBON ATOM-CONTAINING COMPOUND
  申请人：Tani Yuichiro

  公开号：US20090054648A1

  公开（公告）日：2009-02-26

  The invention provides an industrial method for producing a spiroaminopyrrolidone derivative, which is an intermediate for producing a quinolone antibacterial agent. The invention provides a method for producing a compound represented by formula (2): (wherein n is an integer of 2 to 5; R 1 represents a (substituted) alkyl group or a (substituted) aryl group; and R 2 represents a (substituted) alkoxycarbonyl group, a (substituted) aralkyloxycarbonyl group, a (substituted) aliphatic acyl group, or a (substituted) aromatic acyl group), which includes treating a compound represented by formula (1): (wherein n, R 1 , and R 2 are the same as defined above; and R 3 represents a hydrogen atom, a (substituted) alkyl group, or a (substituted) aralkyl group) under a hydrogen gas atmosphere in the presence of a metallic catalyst.

  本发明提供了一种工业方法，用于生产螺环氨基吡咯烷衍生物，该衍生物是生产喹诺酮类抗菌剂的中间体。本发明提供了一种生产由式（2）表示的化合物的方法：（其中n是2至5的整数；R1表示（取代）烷基或（取代）芳基；R2表示（取代）烷氧羰基，（取代）芳基烷氧羰基，（取代）脂肪酰基或（取代）芳香酰基），其包括在金属催化剂存在下，在氢气气氛下处理由式（1）表示的化合物：（其中n，R1和R2如上定义；R3表示氢原子，（取代）烷基或（取代）芳基烷基）。
• US7928232B2
  申请人：——

  公开号：US7928232B2

  公开（公告）日：2011-04-19
• US8138352B2
  申请人：——

  公开号：US8138352B2

  公开（公告）日：2012-03-20
• US8378119B2
  申请人：——

  公开号：US8378119B2

  公开（公告）日：2013-02-19
• Design, Synthesis, and Biological Evaluations of Novel 7-[7-Amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-8-methoxyquinolines with Potent Antibacterial Activity against Respiratory Pathogens
  作者：Takashi Odagiri、Hiroaki Inagaki、Yuichi Sugimoto、Masatoshi Nagamochi、Rie N. Miyauchi、Junichi Kuroyanagi、Takahiro Kitamura、Satoshi Komoriya、Hisashi Takahashi

  DOI：10.1021/jm301650g

  日期：2013.3.14

  Novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]- 8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 2a and 2b were designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Among these, compound 2a possessing (S)-configuration for the asymmetrical carbon on the pyrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens including Gram-positive (Streptococcus pneumoniae and Staphylococcus aureus), Gram-negative (Haemophilus influenzae and Moraxcella catarrhalis), and atypical strains (Chalmydia pneumoniae and Mycoplasma pneumoniae), as well as multidrug-resistant Streptococcus pneumoniae and quinolone-resistant and methicillin-resistant Staphylococcus aureus). Furthermore, compound 2a showed excellent in vivo activity against the experimental murine pneumonia model due to multidrug resistant Streptococcus pneumoniae (MDRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies.