(±)-2-[1-(7-chloro-1,8-naphthyridin-2-ylamino)-6-methyl-3-oxoheptyl]benzoic acid | 147031-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (±)-2-[1-(7-chloro-1,8-naphthyridin-2-ylamino)-6-methyl-3-oxoheptyl]benzoic acid
• 英文别名: (+/-)-2-{1-[(7-chloro-1,8-naphthyridin-2-yl)amino]-6-methyl-3-oxoheptyl}benzoic acid；rac-2-[1-(7-chloro-1,8-naphthyridin-2-ylamino)-6-methyl-3-oxo-heptyl]-benzoic acid；2-{1-[(7-chloro-1,8-naphthyridin-2-yl)amino]-6-methyl-3-oxoheptyl}benzoic acid；2-[1-[(7-chloro-1,8-naphthyridin-2-yl)amino]-6-methyl-3-oxoheptyl]benzoic acid
• CAS: 147031-30-9；147031-31-0；147119-50-4
• 化学式: C₂₃H₂₄ClN₃O₃
• 分子量: 425.915
• InChiKey: MGRYQDGXHUMZKH-UHFFFAOYSA-N

物化性质

• 熔点：
  173-174 °C
• 沸点：
  622.4±55.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (±)-2-[1-(7-chloro-1,8-naphthyridin-2-ylamino)-6-methyl-3-oxoheptyl]benzoic acid 在 麻黄素 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3S-(5-methyl-2-oxohexyl)-1-isoindolinone
  参考文献：
  名称：

  An Efficient and Cost-Effective Synthesis of Pagoclone

  摘要：

  The compound (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3S-(5-methyl-2-oxohexyl)-1-isoindolinone (pagoclone) shows anxiolytic activity due to partial agonism of the benzodiazepine site of the GABA(A) receptor. We describe the development of an economical and practical process for a 100+ kg pilot plant production used to supply development needs. For the key reaction, a beta-keto phosphonium salt was prepared by selectively reacting a primary alpha-bromo ketone with triphenylphosphine in the presence of a secondary alpha-bromo ketone. A novel Wittig reaction with a 1-isoindolinone was used to produce racemic pagoclone. The enantiomerically pure drug substance was prepared by hydrolyzing a gamma-lactam and resolving the resulting enantiomeric carboxylic acids with (+)-ephedrine hemihydrate. An alternate resolution, involving chiral multicolumn chromatography (MCC) was also developed. The synthesis was completed by a racemization-free lactam formation to afford pagoclone.

  DOI：

  10.1021/op034060b
• 作为产物：
  描述：

  2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-3H-isoindol-1-one 生成 (±)-2-[1-(7-chloro-1,8-naphthyridin-2-ylamino)-6-methyl-3-oxoheptyl]benzoic acid
  参考文献：
  名称：

  Heterocyclic compounds

  摘要：

  式子为：##STR1## 其中吡咯烃环和符号R.sub.1和R.sub.2共同形成异吲哚啉、6,7-二氢-5H-吡咯并[3,4-b]吡嗪、2,3,6,7-四氢-5H-1,4-噁嗪并[2,3-c]吡咯或2,3,6,7-四氢-5H-1,4-二噻吩并[2,3-c]吡咯核，Het代表可选取代的吡啶-2-基、喹啉-2-基或1,8-萘啉-2-基基团，Z代表氧或硫，R代表氢、烷基或卤代烷基、烯基、炔基、环烷基、烷氧基、可选取代的苯基、苯基烷基，其中苯环可选取代，苯基烯基，其中苯环可选取代，或R代表含有一或两个氮、氧和硫杂原子的5-或6-成员杂环基团，当吡咯烃环和符号R.sub.1和R.sub.2共同形成异吲哚啉核时，由R.sub.1和R.sub.2表示的异吲哚啉核残基可选取代，具有药理学特性，特别适用于镇静剂、抗惊厥剂、解痉剂和产生催眠作用的剂。

  公开号：

  US04220646A1

文献信息

• 2-amino naphthyridine derivative, its preparation and its use
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05498716A1

  公开（公告）日：1996-03-12

  The present invention relates to a novel 2-aminonaphthyridine compounds that are useful in preparing a 2-isoindolinyl napthyridine compound that exhibits remarkable anxiolytic, hypnotic, anticonvulsant, antiepileptic and muscle-relaxant properties. The invention is also directed to the optical isomers of the 2-amino napthyridine compounds and salts thereof, their preparation and the use of the 2-amino napthyridine compounds for preparing the 2-isoindolinyl napthyridine compound.

  本发明涉及一种新型的2-氨基萘啶化合物，该化合物在制备一种表现出显著抗焦虑、催眠、抗抽搐、抗癫痫和肌肉松弛特性的2-异吲哚啉基萘啶化合物中具有用途。本发明还涉及2-氨基萘啶化合物的光学异构体及其盐，它们的制备以及用于制备2-异吲哚啉基萘啶化合物的2-氨基萘啶化合物的用途。
• Methods for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone
  申请人：——

  公开号：US20030191315A1

  公开（公告）日：2003-10-09

  The present invention relates to methods for making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone.

  本发明涉及制备外消旋2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮和(+)-2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮的方法。
• Pyrrole derivatives, and pharmaceutical compositions which contain them
  申请人：Rhone-Poulenc Sante

  公开号：US04960779A1

  公开（公告）日：1990-10-02

  Pyrrole derivatives of formula (I): ##STR1## in which A forms with the pyrrole ring an isoindoline, 6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine, 2,3,6,7-tetrahydro-5H-[1,4]oxathiino[2,3-c]pyrrole or 2,3,6,7-tetrahydro-5H-[1,4]dithiino[2,3-c]pyrrole ring-system, Het.dbd.naphthyridinyl, pyridyl or quinolyl which are unsubstituted or substituted with halogen, (1 to 4 C) alkyl, (1 to 4 C) alkyloxy, (1 to 4 C) alkylthio or CF.sub.3, Y.dbd.CO, C.dbd.NOH or CHOH and R.dbd.(3 to 10 C) alkenyl, alkyl which is unsubstituted or substituted with OH, alkyloxy, alkylthio, (3 to 6 C) cycloalkyl, NH.sub.2, alkylamino, dialkylamino, alkylcarbonylamino, piperazinyl, piperidyl, 1-azetidinyl, morpholino, pyrrolidinyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, (1-piperazinyl)carbonyl, piperidinocarbonyl, pyrrolidinocarbonyl, phenyl, pyridyl, 1-imidazolyl or alternatively R.dbd.2- or 3-pyrrolididnyl, 2-, 3- or 4-piperidyl, (3 to 6 C) cycloalkyl or phenyl which is unsubstituted or substituted with halogen, (1 to 4 C) alkyl, (1 to 4 C) alkyloxy, (1 to 4 C) alkylthio, the said alkyl radicals and portions containing, except where specifically stated, 1 to 10 C, and the piperazinyl, piperidino, piperidyl, pyrrolidinyl, azetidinyl radicals being unsubstituted or substituted at any position by alkyl, alkylcarbonyl, benzyl or hydroxyalkyl, or can alternatively form a lactam group with the nitrogen atom of the ring, and their salts and optical isomers are useful as anxiolytics.

  公式（I）的吡咯衍生物：##STR1## 其中A与吡咯环形成异吲哚啉，6,7-二氢-5H-吡咯[3,4-b]吡嗪，2,3,6,7-四氢-5H-[1,4]噁嗪并[2,3-c]吡咯或2,3,6,7-四氢-5H-[1,4]二噻并[2,3-c]吡咯环系，Het.dbd.naphthyridinyl，吡啶基或喹啉基，它们未被取代或被卤素，（1至4C）烷基，（1至4C）烷氧基，（1至4C）烷硫基或CF.sub.3取代，Y.dbd.CO，C.dbd.NOH或CHOH，R.dbd.（3至10C）烯基，未被取代或被取代为OH，烷氧基，烷硫基，（3至6C）环烷基，NH.sub.2，烷基氨基，二烷基氨基，烷基羰基氨基，哌嗪基，哌啶基，1-氮杂丙烷基，吗啉基，吡咯啉基，氨基甲酰基，烷基氨甲酰基，二烷基氨甲酰基，（1-哌嗪基）羰基，哌啶基羰基，吡咯啉基羰基，苯基，吡啶基，1-咪唑基，或者R.dbd.2-或3-吡咯烷基，2-，3-或4-哌嗪基，（3至6C）环烷基或未被取代或被卤素，（1至4C）烷基，（1至4C）烷氧基，（1至4C）烷硫基取代的苯基，所述烷基基团和部分含有，除非特别说明，1至10C，哌嗪基，哌啶基，哌嗪基，吡咯啉基，氮杂丙烷基未被取代或被取代为烷基，烷基羰基，苄基或羟基烷基，或者可以与环的氮原子形成内酰胺基团，它们的盐和光学异构体可用作抗焦虑剂。
• Methods for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2oxo-hexyl)-1-isoidolinone
  申请人：Jennings Marie Sandra

  公开号：US20050288322A1

  公开（公告）日：2005-12-29

  The present invention relates to methods for making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone.

  本发明涉及制备外消旋2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮和(+)-2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮的方法。
• Method for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone)
  申请人：Jennings Marie Sandra

  公开号：US20060194830A1

  公开（公告）日：2006-08-31

  The present invention relates to methods for making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone.

  本发明涉及制备外消旋2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮和(+)2-(7-氯-1,8-萘啶基)-3-(5-甲基-2-氧代己基)-1-异吲哚酮的方法。