2,3-二氢-1,4-苯并二氧杂环己烷-2-甲酰氯 | 401947-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 中文名称: 2,3-二氢-1,4-苯并二氧杂环己烷-2-甲酰氯
• 英文名称: (S)-1,4-benzodioxan-2-carbonyl chloride
• 英文别名: (S)-2,3-dihydrobenzo[b][1,4]dioxine-2-carbonyl chloride；(3S)-2,3-dihydro-1,4-benzodioxine-3-carbonyl chloride
• CAS: 401947-96-4
• 化学式: C₉H₇ClO₃
• 分子量: 198.606
• InChiKey: UPCGTFBXZKCPOT-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-二氢-1,4-苯并二氧杂环己烷-2-甲酰氯 在 盐酸 作用下， 以 甲醇 、 水 、 正丁醇 为溶剂， 反应 8.5h， 生成 (S)-doxazosin hydrochloride
  参考文献：
  名称：

  Practical chemical and enzymatic technologies for (S)-1,4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate

  摘要：

  (S)-1,4-Benzodioxan-2-carboxypiperazine (S)-2, the key chiral intermediate for the synthesis of (S)-doxazosin, was prepared utilizing two approaches: (i) enzymatic resolution of ethyl 1,4-benzodioxan-2-carboxylate with an esterase (Serratia) followed by an-de formation; (ii) direct resolution of 1,4-benzodioxan-2-carboxypiperazine 2 with D-tartaric acid. An efficient process for the conversion of (S)-2 to (S)-doxazosin mesylate was developed (80% yield, 99.9% e.e.). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00368-8
• 作为产物：
  描述：

  1,4-苯并二氧六环-2-甲酸乙酯 在 sodium hydroxide 、 氯化亚砜 、 esterase from Serracia marcescens 、 碳酸氢钠 作用下， 以 氘代氯仿 、 甲苯 为溶剂， 反应 21.0h， 生成 2,3-二氢-1,4-苯并二氧杂环己烷-2-甲酰氯
  参考文献：
  名称：

  Practical chemical and enzymatic technologies for (S)-1,4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate

  摘要：

  (S)-1,4-Benzodioxan-2-carboxypiperazine (S)-2, the key chiral intermediate for the synthesis of (S)-doxazosin, was prepared utilizing two approaches: (i) enzymatic resolution of ethyl 1,4-benzodioxan-2-carboxylate with an esterase (Serratia) followed by an-de formation; (ii) direct resolution of 1,4-benzodioxan-2-carboxypiperazine 2 with D-tartaric acid. An efficient process for the conversion of (S)-2 to (S)-doxazosin mesylate was developed (80% yield, 99.9% e.e.). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00368-8

文献信息

• Heterocycloalkylbenzocyclobutane and heteroarylbenzocyclobutane compounds
  申请人：——

  公开号：US20020019380A1

  公开（公告）日：2002-02-14

  A compound selected from those of formula (I): 1 wherein: overscore (_____)} denotes single bond or double bond, n is integer from 1 to 6 inclusive, R 1 , and R 2 represent a group selected from hydrogen, linear or branched (C 1 -C 6 )-alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, X represents a group selected from —CH═CH—, oxygen, S(O) m wherein m is integer from 0 to 2 inclusive, and NR 3 wherein R 3 represents a group as defined in the description, Y represents CH or CH 2 depending on whether _____ denotes single bond or double bond, or may have the additional meaning of oxygen when X represents oxygen, T represents monocyclic or polycyclic (C 3 -C 10 )cycloalkyl optionally containing within the ring system oxygen, selenium, S(O) p , NR 3 , or SiR 4 R 5 wherein p, R 3 , R 4 , and R 5 are as defined in the description, its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same are useful in the treatment of CNS disorders.

  从以下通式（I）的化合物中选择的一种化合物：1其中：overscore (_____)}表示单键或双键，n是1至6（含）的整数，R1和R2表示从氢、直链或支链（C1-C6）-烷基、芳基、芳基烷基、环烷基、环烷基烷基、烯基、炔基、杂环烷基、杂环烷基烷基、杂芳基和杂芳基烷基中选择的基团，X表示从—CH═CH—、氧、S(O)m（其中m是0至2（含）的整数）和NR3（其中R3表示如说明书中定义的基团）中选择的基团，Y表示CH或CH2取决于_____表示单键或双键，或者当X表示氧时，Y还可以有氧的含义，T表示含或不含环系统内氧、硒、S(O)p、NR3或SiR4R5的单环或多环（C3-C10）环烷基（其中p、R3、R4和R5如说明书中定义），其异构体和与药学上可接受的酸或碱形成的加成盐，以及含有这些化合物的药物制剂，可用于治疗中枢神经系统疾病。
• How do reaction conditions affect the enantiopure synthesis of 2-substituted-1,4-benzodioxane derivatives?
  作者：Valentina Straniero、Andrea Casiraghi、Laura Fumagalli、Ermanno Valoti

  DOI：10.1002/chir.22968

  日期：2018.7

  biologically active compounds structurally include the enantiopure 2‐substituted‐1,4‐benzodioxane scaffold. The straightforward racemization that affects reactions involving most of the common chemical reactives is thus a crucial issue. The developing of a completely stereo‐controlled synthetic route that does not affect the enantiomeric excess is consequently mandatory. It is also important to set up a reliable

  几种具有生物活性的化合物在结构上包括对映体2-取代-1,4-苯并二恶烷骨架。因此，影响涉及大多数常见化学反应物的反应的直接外消旋作用是至关重要的问题。因此，必须开发一种不影响对映体过量的完全立体控制的合成路线。建立可靠的手性HPLC方法，使其能够追踪反应并改善合成性能也很重要。在这里，我们报告了两种不同合成子的手性研究，我们专门评估了可以运行的合成途径以提供它们，从而避免了通常在碱性条件下可能发生的外消旋过程。此外，我们开发了独特的手性HPLC方法来拆分对映体，
• ARYL PIPERAZINE AND THEIR USE AS ALPHA2C ANTAGONISTS
  申请人：Din Belle David

  公开号：US20110262352A1

  公开（公告）日：2011-10-27

  Compounds of formula (I), wherein X, Z, A, B, D, E, R 1 -R 4 and m are as defined in the claims, exhibit alpha2C antagonistic activity and are thus useful as alpha2 antagonists.

  式(I)的化合物，其中X、Z、A、B、D、E、R1-R4和m如权利要求所定义，表现为α2C拮抗活性，因此可用作α2拮抗剂。
• 2,4-Diamino-6,7-dimethoxyquinazolines. 1. 2-[4-(1,4-Benzodioxan-2-ylcarbonyl)piperazin-1-yl] derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents
  作者：Simon F. Campbell、Michael J. Davey、J. David Hardstone、Brian N. Lewis、Michael J. Palmer

  DOI：10.1021/jm00384a009

  日期：1987.1

  A series of 4-amino-2-[4-(1,4-benzodioxan-2-ylcarbonyl)piperazin-1 -yl]-6, 7-dimethoxyquinazoline derivatives was synthesized for evaluation as alpha-antagonists and antihypertensive agents. Most compounds displayed high (nM) binding affinity for alpha 1-adrenoceptors with no significant activity at alpha 2-sites. Selective antagonism of the alpha 1-mediated vasoconstrictor effects of norepinephrine is also characteristic of the series. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented, and structural similarity between the 2,4-diamino-6,7-dimethoxyquinazoline nucleus and norepinephrine is established. An alpha 1-receptor model is presented in which charge-reinforced hydrogen bonding is important for binding of both antagonist and agonist molecules. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and several compounds displayed similar efficacy to prazosin when assessed after 6 h. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compound 1 (doxazosin) was selected for further evaluation and is currently progressing through phase III clinical trials.
• Quinazoline based α 1 -adrenoreceptor antagonists with potent antiproliferative activity in human prostate cancer cell lines
  作者：Valentina Maestri、Andrea Tarozzi、Elena Simoni、Antonio Cilia、Elena Poggesi、Marina Naldi、Benedetta Nicolini、Letizia Pruccoli、Michela Rosini、Anna Minarini

  DOI：10.1016/j.ejmech.2017.05.003

  日期：2017.8

  New alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists related to prazosin and doxazosin were synthesized by replacing piperazine ring with (S)- or (R)-3-aminopiperidine. Binding studies indicated that the S configuration at the 3-C position of the piperidine ring is crucial for an optimal interaction of the compounds at all three alpha(1)-AR subtypes. Quinazolines 9 and 10, bearing a quinone ring on the lateral chain, exhibited also potent antiproliferative activity in LNCaP androgen-sensitive prostate cancer cell lines, higher than that of doxazosin. Compound 10 increased apoptosis, in terms of DNA fragmentation, without triggering cell necrosis. The prooxidant activity found in compound 10 may underlie its ability to inhibit cell proliferation in synergy with the effect mediated by alpha(1)-AR antagonism. Due to its better biological profile compared to doxazosin for LNCaP cell line, compound 10 might be a valuable lead compound for the design of new prostate antitumor agents. (C) 2017 Elsevier Masson SAS. All rights reserved.