5,6,7,8-tetrahydro-2,4-di-1-pyrrolidinyl-1H-pyrimido[4,5-b]indole | 157013-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,6,7,8-tetrahydro-2,4-di-1-pyrrolidinyl-1H-pyrimido[4,5-b]indole
• 英文别名: 2,4-Di(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indole；2,4-dipyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indole
• CAS: 157013-25-7
• 化学式: C₁₈H₂₅N₅
• 分子量: 311.43
• InChiKey: HATSQPGGZVMIDL-UHFFFAOYSA-N

物化性质

• 密度：
  1.275±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  48
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6,7,8-tetrahydro-2,4-di-1-pyrrolidinyl-1H-pyrimido[4,5-b]indole 在 palladium 10% on activated carbon 、 萘烷 作用下， 反应 74.0h， 以43%的产率得到2,4-di-1-pyrrolidinyl-5H-pyrimido[4,5-b]indole
  参考文献：
  名称：

  Synthesis of 2,4-Di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indoles, Including Antiasthma Clinical Candidate PNU-142731A

  摘要：

  Two syntheses are described for 1-[(2,4.di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indol-9-yl)-acetyl]pyrrolidine hydrochloride (PNU-142731A), a clinical candidate in the asthma area. The route involving the initial regioselective addition of glycine ethyl ester to commercially available 2,4,6-trichloropyrimidine is particularly well suited for large-scale operation, as it is short, proceeds in good yield, is operationally straightforward, and requires no chromatographic purification of intermediates.

  DOI：

  10.1021/op000221p
• 作为产物：
  描述：

  2-溴环己酮 、 2,6-二吡咯烷-1-基嘧啶-4-胺 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以26%的产率得到5,6,7,8-tetrahydro-2,4-di-1-pyrrolidinyl-1H-pyrimido[4,5-b]indole
  参考文献：
  名称：

  Synthesis of 2,4-Di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indoles, Including Antiasthma Clinical Candidate PNU-142731A

  摘要：

  Two syntheses are described for 1-[(2,4.di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indol-9-yl)-acetyl]pyrrolidine hydrochloride (PNU-142731A), a clinical candidate in the asthma area. The route involving the initial regioselective addition of glycine ethyl ester to commercially available 2,4,6-trichloropyrimidine is particularly well suited for large-scale operation, as it is short, proceeds in good yield, is operationally straightforward, and requires no chromatographic purification of intermediates.

  DOI：

  10.1021/op000221p

文献信息

• PHARMACEUTICALLY ACTIVE BICYCLIC-HETEROCYCLIC AMINES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0633886B1

  公开（公告）日：2000-10-18
• US5502187A
  申请人：——

  公开号：US5502187A

  公开（公告）日：1996-03-26
• [EN] PHARMACEUTICALLY ACTIVE BICYCLIC-HETEROCYCLIC AMINES<br/>[FR] AMINES BICYCLIQUES-HETEROCYCLIQUES EFFICACES PHARMACEUTIQUEMENT
  申请人：THE UPJOHN COMPANY

  公开号：WO1993020078A1

  公开（公告）日：1993-10-14

  (EN) The pharmaceutically active bicyclic heterocyclic amines (XXX), where W1 is -N= or -CH=; W3 is -N= or -CH=; W5 is -N= or -CR5- with the proviso that W5 is -CR5- when both W1 and W3 are -N= which are useful as pharmaceuticals in treating mild and/or moderate to severe head injury, subarachnoid hemorrhage and subsequent ischemic stroke, asthma and reduction of mucous formation/secretion in the lung and other diseases and injuries.(FR) Amines bicycliques hétérocycliques efficaces pharmaceutiquement et représentées par la formule (XXX), dans laquelle W1 représente -N= ou -CH=; W3 représente -N= ou -CH=; W5 représente -N= ou -CR5- dans la mesure où W5 représente -CR5- quand à la fois W1 et W3 représentent -N=. Lesdites amines sont efficaces en tant que produits pharmaceutiques dans le traitement de traumatismes craniens bénins et/ou modérés à graves, d'hémorragies sous-arachnoïdiennes et ictus ischémiques subséquents, de l'asthme et de la diminution de la formation/sécrétion muqueuse dans le poumon, ainsi que d'autres maladies et lésions.
• Synthesis of 2,4-Di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indoles, Including Antiasthma Clinical Candidate PNU-142731A
  作者：Gordon L. Bundy、Lee S. Banitt、Paul J. Dobrowolski、John R. Palmer、Theresa M. Schwartz、David C. Zimmermann、Michael F. Lipton、Michael A. Mauragis、Michael F. Veley、Robert B. Appell、Robert C. Clouse、Edward D. Daugs

  DOI：10.1021/op000221p

  日期：2001.3.1

  Two syntheses are described for 1-[(2,4.di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indol-9-yl)-acetyl]pyrrolidine hydrochloride (PNU-142731A), a clinical candidate in the asthma area. The route involving the initial regioselective addition of glycine ethyl ester to commercially available 2,4,6-trichloropyrimidine is particularly well suited for large-scale operation, as it is short, proceeds in good yield, is operationally straightforward, and requires no chromatographic purification of intermediates.