1-(S)-1-(2,3-dihydrobenzofuran-5-yl)-2,3,4,9-tetrahydro-1H-β-carboline | 199680-17-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-(S)-1-(2,3-dihydrobenzofuran-5-yl)-2,3,4,9-tetrahydro-1H-β-carboline
• 英文别名: (1S)-1-(2,3-dihydrobenzofuran-5-yl)-2,3 ,4,9-tetrahydro-1H-β-carboline；(1S)-1-(2,3-dihydro-1-benzofuran-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• CAS: 199680-17-6
• 化学式: C₁₉H₁₈N₂O
• 分子量: 290.365
• InChiKey: RQEHSDWWBXNMPR-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2,3-二氢苯并呋喃-5-甲醛 在 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 37.17h， 生成 1-(S)-1-(2,3-dihydrobenzofuran-5-yl)-2,3,4,9-tetrahydro-1H-β-carboline 、 1-(R)-1-(2,3-dihydrobenzofuran-5-yl)-2,3,4,9-tetrahydro-1H-β-carboline
  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

• 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：——
• CARBOLINE DERIVATIVES
  申请人：ICOS CORPORATION

  公开号：EP0912567B1

  公开（公告）日：2002-04-10
• US6043252A
  申请人：——

  公开号：US6043252A

  公开（公告）日：2000-03-28
• US6117881A
  申请人：——

  公开号：US6117881A

  公开（公告）日：2000-09-12