6-氯-2,3-二氢-5-甲氧基-1H-茚-1-酮 | 475654-43-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 6-氯-2,3-二氢-5-甲氧基-1H-茚-1-酮
• 英文名称: 6-chloro-5-methoxyindan-1-one
• 英文别名: 6-chloro-5-methoxy-2,3-dihydro-1H-inden-1-one；6-chloro-5-methoxy-2,3-dihydroinden-1-one
• CAS: 475654-43-4
• 化学式: C₁₀H₉ClO₂
• 分子量: 196.633
• InChiKey: LQTCWWPSORPTSP-UHFFFAOYSA-N

物化性质

• 沸点：
  340.6±42.0 °C(Predicted)
• 密度：
  1.302

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-氯-2,3-二氢-5-甲氧基-1H-茚-1-酮 在 1-氯乙基氯甲酸酯 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.67h， 生成 tert-butyl 6-chloro-5-methoxy-1-oxo-1,3-dihydrospiro[indene-2,4’-piperidine]-1’-carboxylate
  参考文献：
  名称：

  WO2020201991A5

  摘要：

  公开号：

  WO2020201991A5
• 作为产物：
  描述：

  3-氯-4-甲氧基苯甲醛 在 platinum(IV) oxide 哌啶 、 吡啶 、 三氯化铝 、 氯化亚砜 、 氢气 作用下， 以 甲醇 、 二硫化碳 为溶剂， 20.0~115.0 ℃ 、100.0 kPa 条件下， 反应 13.67h， 生成 6-氯-2,3-二氢-5-甲氧基-1H-茚-1-酮
  参考文献：
  名称：

  Synthesis and preliminary pharmacological evaluation of trans-2-amino-5(6)-chloro-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes as dopamine receptor ligands

  摘要：

  A series of trans-2-amino-5(6)-chloro-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes were synthesized and evaluated for their binding affinity toward D-1-like and D-2-like dopamine (DA) receptors. The affinity and selectivity of these compounds were measured in a test involving displacement of [H-3]SCH 23390 or [H-3]YM-09-151-2, respectively, from homogenates of porcine striatal membranes. All tested compounds were poorly effective at DA receptors (K-i nM > 1000). The results suggest that introduction of chlorine substituent in five or six position of previously synthesized trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes decreases both D-1-like and D-2-like receptor affinity. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

  DOI：

  10.1016/s0014-827x(02)01206-5

文献信息

• Use of Fluoroalkyl as a Latent Group for Internal Alkylation: Application to the Synthesis of Bridged Tetrahydrofluorenones
  作者：Dann L. Parker, Jr.、Amy K. Fried、Dongfang Meng、Mark L. Greenlee

  DOI：10.1021/ol800971f

  日期：2008.7.17

  Tetrahydrofluorenones which possess a C9a-fluoroalkyl substituent were efficiently converted to tetrahydrofluorenones which contain a ring bridging C9a-C2. Conditions include a stepwise sequence of conversion to an alkyl bromide followed by treatment with base, and a direct cyclization by treatment with lithium chloride in DMF heated to 150 degrees C.

  具有C9a-氟烷基取代基的四氢​​芴酮被有效地转化为含有环桥C9a-C2的四氢芴酮。条件包括逐步转化为烷基溴的顺序，然后用碱处理，以及通过在加热至150摄氏度的DMF中用氯化锂处理直接环化。
• Development of a Phase Transfer Catalyzed Asymmetric Synthesis for an Estrogen Receptor Beta Selective Agonist
  作者：Jeremy P. Scott、Michael S. Ashwood、Karel M. J. Brands、Sarah E. Brewer、Cameron J. Cowden、Ulf-H. Dolling、Khateeta M. Emerson、Andrew D. Gibb、Adrian Goodyear、Steven F. Oliver、Gavin W. Stewart、Debra J. Wallace

  DOI：10.1021/op700178q

  日期：2008.7.1

  A practical asymmetric synthesis of the estrogen receptor beta selective agonist (7β-9aβ)-1,4-dichloro-2-hydroxygibba-1(10a),2,4,4b-tetraen-6-one (1), proceeding by way of six isolated intermediates and without recourse to chromatography, is described. Highlights of the process route developed are two chemoselective chlorinations, a lithiated hydrazone alkylation and an asymmetric Michael addition

  实用的不对称合成雌激素受体β选择性激动剂（7β-9aβ）-1,4-dichloro-2-hydroxygibba-1（10a），2,4,4b-tetraen-6-one（1）进行描述了六种分离的中间体，无需借助色谱法。所开发工艺路线的重点是两次化学选择性氯化，锂化烷基化和在甲基乙烯基酮中使用茚满酮11的不对称迈克尔加成反应（使用15 mol％的辛可宁衍生催化剂20g）设置全碳四元不对称立体中心。详细讨论了将后者的异相双相转移反应规模扩展至44 mol（14 kg）规模时所面临的挑战。总体而言，开发的化学方法已用于制备> 6 kg候选药物1，总产率为18％，ee≥99％。
• Estrogen Receptor Modulators
  申请人：Greenlee L. Mark

  公开号：US20070265318A1

  公开（公告）日：2007-11-15

  The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget's disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, age-related mild cognitive impairment, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease, irritable bowel syndrome, sexual dysfunction, hypertension, retinal degeneration and cancer, in particular of the breast, uterus and prostate.

  本发明涉及化合物及其衍生物、它们的合成以及它们作为雌激素受体调节剂的用途。本发明的化合物是雌激素受体的配体，因此可能有助于治疗或预防与雌激素功能相关的多种疾病，包括：骨质流失、骨折、骨质疏松症、转移性骨病、帕吉特病、牙周病、软骨退化、子宫内膜异位症、子宫肌瘤疾病、潮热、低密度脂蛋白胆固醇水平升高、心血管疾病、认知功能障碍、年龄相关的轻度认知障碍、脑退行性疾病、再狭窄、男性乳房发育、血管平滑肌细胞增殖、肥胖症、失禁、炎症、炎性肠病、肠易激综合征、性功能障碍、高血压、视网膜退化和癌症，特别是乳腺、子宫和前列腺癌。
• Estrogen receptor modulators
  申请人：Merck & Co., Inc.

  公开号：US07511152B2

  公开（公告）日：2009-03-31

  The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget's disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, age-related mild cognitive impairment, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease, irritable bowel syndrome, sexual dysfunction, hypertension, retinal degeneration and cancer, in particular of the breast, uterus and prostate.

  本发明涉及化合物及其衍生物、它们的合成以及它们作为雌激素受体调节剂的用途。本发明的化合物是雌激素受体的配体，因此可能用于治疗或预防与雌激素功能相关的各种疾病，包括：骨质流失、骨折、骨质疏松症、转移性骨病、帕吉特病、牙周病、软骨退化、子宫内膜异位症、子宫肌瘤疾病、潮热、低密度脂蛋白胆固醇水平升高、心血管疾病、认知功能受损、年龄相关的轻度认知功能障碍、脑部退化性疾病、再狭窄、男性乳腺发育、血管平滑肌细胞增殖、肥胖症、失禁、炎症、炎性肠病、肠易激综合征、性功能障碍、高血压、视网膜退化和癌症，特别是乳腺、子宫和前列腺癌。
• Catalytic Asymmetric Inverse‐Electron‐Demand Diels–Alder Reactions of 2‐Pyrones with Indenes: Total Syntheses of Cephanolides A and B
  作者：Yang Lu、Meng‐Meng Xu、Zhi‐Mao Zhang、Junliang Zhang、Quan Cai

  DOI：10.1002/anie.202112223

  日期：2021.12.13

  Catalytic asymmetric all-carbon-based inverse-electron-demand Diels–Alder reactions of 2-pyrones with electronically unbiased indenes have been realized. This method enables the rapid and enantioselective construction of a wide range of hexahydrofluorenyl bridged-lactone scaffolds. Based on this method, asymmetric total syntheses of cephanolides A and B have been accomplished.

  2-吡喃酮与电子无偏茚的催化不对称全碳基逆电子需求 Diels-Alder 反应已经实现。这种方法能够快速和对映选择性地构建范围广泛的六氢芴基桥接内酯支架。基于该方法，完成了头孢内酯A和B的不对称全合成。