(3R)-2-苄基-3-(2,3-二氢-1-苯并呋喃-5-基)-3,4-二氢-1H-吡咯并[3,4-B]喹啉-9-酮 | 374926-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: (3R)-2-苄基-3-(2,3-二氢-1-苯并呋喃-5-基)-3,4-二氢-1H-吡咯并[3,4-B]喹啉-9-酮
• 英文名称: 3-(R)-2-benzyl-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one
• 英文别名: (R)-1,2,3,4-tetrahydro-2-benzyl-3-(2,3-dihydrobenzofuran-5-yl)-9H-pyrrolo-[3,4-b]quinolin-9-one；(3R)-2-benzyl-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one；(3R)-2-benzyl-3-(2,3-dihydro-1-benzofuran-5-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one
• CAS: 374926-62-2
• 化学式: C₂₆H₂₂N₂O₂
• 分子量: 394.473
• InChiKey: VIYBNMCRHNVHRW-RUZDIDTESA-N

物化性质

• 沸点：
  575.5±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R)-2-苄基-3-(2,3-二氢-1-苯并呋喃-5-基)-3,4-二氢-1H-吡咯并[3,4-B]喹啉-9-酮 在 palladium on activated charcoal 氢气 作用下， 生成 (R)-(-)-1,2,3,4-tetrahydro-3-(2,3-dihydrobenzofuran-5-yl)-9H-pyrrolo-[3,4-b]quinolin-9-one
  参考文献：
  名称：

  嘧啶基吡咯并喹诺酮类药物是治疗勃起功能障碍的高效和选择性PDE5抑制剂。

  摘要：

  发现了一系列N-嘧啶基吡咯并喹诺酮类是非常有效和选择性的PDE5抑制剂。代表性化合物在狗勃起功能障碍模型中显示出体内功效，并且可以口服生物利用。

  DOI：

  10.1021/jm025545d
• 作为产物：
  描述：

  2,3-二氢苯并呋喃-5-甲醛 在 potassium superoxide 、 potassium carbonate 、 甲基三丁基氯化铵 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 36.39h， 生成 (3R)-2-苄基-3-(2,3-二氢-1-苯并呋喃-5-基)-3,4-二氢-1H-吡咯并[3,4-B]喹啉-9-酮
  参考文献：
  名称：

  An Efficient Process for Synthesis of 3-(R)-3-(2,3-Dihydrobenzofuran-5-yl)- 1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one

  摘要：

  3-(R)-3-(2,3-Dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one (1) is a key intermediate in the synthesis of pyrroloquinolone analogues, a series of highly potent and selective phosphodiesterase 5 (PDE5) inhibitors. Racemic 1-(2,3-dihydrobenzofuran-5-yl)-2,3,4,9-tetrahydro-1H-beta-carboline (6, Scheme 2) was prepared by Pictet-Spenger condensation in 84% isolated yield with > 97% chemical purity. The desired intermediate, 1-(R)-1-(2,3-dihydrobenzofuran-5-yl)2,3,4,9-tetrahydro-1H-beta-carboline N-acetyl-D-leucine salt (8), was obtained in 35% isolated yield with high chiral purity (> 97% ee) from the chemical resolution of 6 with N-acetyl-D-leucine (7). A racemization step was developed for recycling enriched 1-(S)-beta-carboline 9 freebase (8/9, 25 +/- 3%/75 +/- 3%) to a near racemic mixture (8/9, 47 +/- 1%153 +/- 1%). Furthermore, the resolving reagent 7 was recovered in > 76% yield, which, together with the recycled racemic mixture (8/9, 47 1%153 1%), afforded 35% more salt 8 after two recycles (>= 97.0% ee). The salt 8 was converted to 1-(R)-1-(2,3-dihydrobenzofuran-5-yl)-2-benzyl-2,3,4,9-tetrahydro-1H-beta-carbo- line (10) in excellent yield (94%). A modified Winterfeldt oxidation of compound 10 using Aliquat 175 as a phase transfer catalyst produced 3-(R)-2-benzyl-3-(2,3-dihydrobenzofuran-5yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one (12) in moderate 42% yield. Hydrogenolysis of compound 12 gave the desired compound 1 in quantitative yield with retention of chiral purity (>= 97.0% ee). This efficient, reproducible, economical, and nonchromatography scale-up process could be used to make multikilogram quantities of compound 1.

  DOI：

  10.1021/op050079y

文献信息

• Substituted pyrrolopyridinone derivatives useful as phosphodiesterase inhibitors
  申请人：——

  公开号：US20020010183A1

  公开（公告）日：2002-01-24

  The invention relates to novel pyrrolopyridinone derivatives of the formula (I) or (II): 1 pharmaceutical compositions containing the compounds and their use for the treatment of sexual dysfunction.

  这项发明涉及公式(I)或(II)的新型吡咯吡啶酮衍生物： 1 含有这些化合物的药物组合物及其用于治疗性功能障碍的用途。
• Efficient and stereoselective process for large scale synthesis of (3R)-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one derivatives
  申请人：Li Xun

  公开号：US20070015798A1

  公开（公告）日：2007-01-18

  This invention relates to an efficient process for large scale stereoselective production of (3R)-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-ones and key intermediates used for the preparation of benzofuranyl pyrroloquinolones as potent and selective PDE5 inhibitors for the treatment of erectile dysfunction, as well as pharmaceutical compositions and methods of treatment utilizing these compounds.

  本发明涉及一种有效的大规模立体选择性生产(3R)-3-(2,3-二氢苯并呋喃-5-基)-1,2,3,4-四氢吡咯并[3,4-b]喹啉-9-酮及其在制备苯并呋喃基吡咯喹啉类PDE5抑制剂用作治疗勃起功能障碍的关键中间体方面的应用，以及利用这些化合物的制药组合物和治疗方法。
• WO2006/93719
  申请人：——

  公开号：——

  公开（公告）日：——
• Development of a Scalable and Safe Procedure for the Production of (3<i>R</i>)-3-(2,3-Dihydro-1-benzofuran-5-yl)-1,2,3,4-tetrahydro-9<i>H</i>-pyrrolo[3,4-<i>b</i>]- quinolin-9-one, an Intermediate in the Synthesis of PDE-V Inhibitors RWJ387273 (R301249) and RWJ444772 (R290629)
  作者：Bert Willemsens、Ivan Vervest、Dominic Ormerod、Wim Aelterman、Christine Fannes、Narda Mertens、István E. Markó、Sebastien Lemaire

  DOI：10.1021/op060099f

  日期：2006.11.1

  A scalable and safe process for the oxidative rearrangement of beta-carboline to quinolone derivatives, intermediates in the synthesis of PDE-V inhibitors RWJ387273 (R301249) and RWJ444772 (R290629), has been developed.
• SUBSTITUTED PYRROLOPYRIDINONE DERIVATIVES USEFUL AS PHOSPHODIESTERASE INHIBITORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1296981B1

  公开（公告）日：2004-10-06