3,4-epoxy-6-methoxycarbonyl-2,2-dimethylchroman | 65018-82-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3,4-epoxy-6-methoxycarbonyl-2,2-dimethylchroman
• 英文别名: 6-Carbomethoxy-3,4-dihydro-2,2-dimethyl-3,4-epoxy-2H-benzo[b]pyran；methyl 2,2-dimethyl-1a,7b-dihydrooxireno[2,3-c]chromene-6-carboxylate
• CAS: 65018-82-8
• 化学式: C₁₃H₁₄O₄
• 分子量: 234.252
• InChiKey: APMKKPHGMDRZAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  48.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,4-epoxy-6-methoxycarbonyl-2,2-dimethylchroman 在 ammonium hydroxide 作用下， 以 乙醇 为溶剂， 反应 144.0h， 生成 trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(1-pyrrolidinyl)-2H-1-benzopyran-6-carboxylic acid
  参考文献：
  名称：

  取代的反式-4-氨基-3,4-二氢-2,2-二甲基-2H-1-苯并吡喃-3-醇的合成及降压活性。

  摘要：

  制备了一系列新型取代的反式-4-氨基-3,4-二氢-2,2-二甲基-2H-1-苯并吡喃-3-醇，并在有意识的乙酸脱氧皮质酮（DOCA）/盐水处理中测试了其降压活性。高血压大鼠。最佳的降血压活性需要一个强的吸电子基团与6位上的吡咯烷基或哌啶子基团一起进行6位取代。7-硝基-4-吡咯烷类似物和6-硝基-3-氯丙胺的例外，它们保留了明显的降压活性。所有这些化合物都是直接的血管扩张药，并且具有与肼屈嗪和钙拮抗剂硝苯地平相当的降压活性。这些化合物的合成路线包括将炔丙基醚环化为2H-1-苯并吡喃，然后通过溴代醇转化为3,4-环氧化物，用适当的胺开环。间取代的炔丙基醚在热环化反应中同时产生5-和7-取代的苯并吡喃，前者占优势。描述了一种新的制备2，2-二甲基-7-硝基苯并吡喃的途径。

  DOI：

  10.1021/jm00365a007
• 作为产物：
  描述：

  methyl 2,2-dimethyl-2H-1-benzopyran-6-carboxylate 在 2,6-二甲基吡啶 、 丙醛二乙基乙缩醛 、 bis(3-methyl-2,4-pentanedionato)cobalt(II) 、 4 A molecular sieve 、 氧气 作用下， 45.0 ℃ 、101.32 kPa 条件下， 反应 19.0h， 以78%的产率得到3,4-epoxy-6-methoxycarbonyl-2,2-dimethylchroman
  参考文献：
  名称：

  钴(II)配合物催化分子氧和醛缩醛联用制备烯烃制备酸敏环氧化物的新方法

  摘要：

  通过在常压下分子氧和醛缩醛的协同作用，将相应的烯烃氧化，并在钴催化下，成功地合成了酸敏感环氧化物，如色烯氧化物或γ,δ-不饱和醇的环氧化物（ II) 与 1,3-二酮配体配位的复合物。反应在温和且中性的条件下进行，并以良好的收率获得所需的环氧化物。在本反应条件下，既没有观察到过氧化也没有观察到形成的环氧化物分解。此外，各种甲硅烷基烯醇醚和甲硅烷基烯酮缩醛，酸敏感化合物，也分别顺利地单氧化成相应的 α-羟基酮和 α-羟基羧酸酯。

  DOI：

  10.1246/bcsj.67.2195

文献信息

• Synthesis and antihypertensive activity of 4-(cyclic amido)-2H-1-benzopyrans
  作者：Valerie A. Ashwood、Robin E. Buckingham、Frederick Cassidy、John M. Evans、Erol A. Faruk、Thomas C. Hamilton、David J. Nash、Geoffrey Stemp、Kenneth Willcocks

  DOI：10.1021/jm00161a011

  日期：1986.11

  administered orally to conscious spontaneously hypertensive rats, are described. The effects of lactam ring size, the presence of heteroatoms in the lactam ring, substitution at C(2) and C(3), relative stereochemistry at C(3) and C(4), and aromatic substitution pattern on the blood pressure lowering activity of this series have been determined. The key compound 2 from this work [BRL 34915; (+/-)-6-cyano-3,4-dihydro-2

  描述了口服给有意识的自发性高血压大鼠的一系列新型4-（环酰胺基）-2H-1-苯并吡喃-3-醇的合成和降压活性。内酰胺环大小，内酰胺环中杂原子的存在，在C（2）和C（3）处的取代，在C（3）和C（4）处的相对立体化学以及芳香族取代模式对血压降低的影响该系列的活性已经确定。这项工作的关键化合物2 [BRL 34915; （（+/-）-6-氰基-3,4-二氢-2,2-二甲基-反-4-（2-氧吡咯烷-1-基）-2H-1-苯并吡喃-3-醇]已经解决，发现降压活性主要存在于（-）对映体中。制备这类化合物的关键步骤是环酰胺阴离子对适当环氧化物的作用。另一种方法
• Benzopyrans
  申请人：Beecham Group p.l.c.

  公开号：US04446113A1

  公开（公告）日：1984-05-01

  Compounds of formula (I): ##STR1## wherein: one of R.sub.1 and R.sub.2 is hydrogen and the other is selected from the class of alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, alkylsulphinyl, alkylsulphonyl, alkoxysulphinyl, alkoxysulphonyl, alkylcarbonylamino, alkoxycarbonylamino, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two alkyl groups, or alkylsulphinylamino, alkylsulphonylamino, alkoxysulphinylamino or alkoxysulphonylamino, or ethylenyl terminally substituted by alkylcarbonyl, nitro or cyano or --C(alkyl)NOH or --C(alkyl)NNH.sub.2, the alkyl groups or alkyl moieties of alkyl-containing groups having from 1 to 6 carbon atoms; one of R.sub.3 and R.sub.4 is hydrogen or alkyl having from 1 to 4 carbon atoms and the other is alkyl having from 1 to 4 carbon atoms, or R.sub.3 and R.sub.4 together with the carbon atom to which they are attached are spiroalkyl having from 3 to 6 carbon atoms; R.sub.5 is hydrogen, alkyl having from 1 to 3 carbon atoms or acyl having from 1 to 8 carbon atoms; and n is 1 or 2; the lactam group being trans to the OR.sub.5 group; have anti-hypertensive activity and are of use in the treatment of high blood pressure.

  式（I）的化合物：其中：R.sub.1和R.sub.2中的一个是氢，另一个选自烷基羰基、烷氧羰基、烷基羟基甲基、硝基、氰基、氯基、三氟甲基、烷基砜基、烷基磺酰基、烷氧基砜基、烷氧基磺酰基、烷基羰胺基、烷氧羰胺基，或氨基砜基、氨基磺酰基或氨基羰基类别，氨基团可选地被一个或两个烷基基团取代，或者烷基砜基氨基、烷基磺酰基氨基、烷氧基砜基氨基或烷氧基磺酰基氨基，或者末端取代为烷基羰基、硝基或氰基或--C（烷基）NOH或--C（烷基）NNH.sub.2的乙烯基，烷基含有1至6个碳原子的烷基基团；R.sub.3和R.sub.4中的一个是氢或含有1至4个碳原子的烷基，另一个是含有1至4个碳原子的烷基，或者R.sub.3和R.sub.4与它们连接的碳原子一起是含有3至6个碳原子的螺环烷基；R.sub.5是氢、含有1至3个碳原子的烷基或含有1至8个碳原子的酰基；n为1或2；内酰胺基团位于OR.sub.5基团的反位；具有降压活性，并可用于治疗高血压。
• Synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and related compounds, new potassium channel activators
  作者：Rolf Bergmann、Rolf Gericke

  DOI：10.1021/jm00164a005

  日期：1990.2

  other heterocycles such as 4-pyridone, pyrimidone, pyridazinone, pyrazinone, and 1,4-butanesultam, the activity is maintained. The removal of the 3-hydroxy function (----17a) does not significantly reduce the activity. The elimination of water from the chromanols leads to the formation of the chromenes, which are among the most potent antihypertensives known. The influence of diverse substituents, in

  描述了4-（1,2-二氢-2-氧代-1-吡啶基）-2H-1-苯并吡喃-3-醇的合成和降压活性。未取代的吡啶酮加合物铅化合物7e具有高活性，吡啶酮环上的取代基导致活性降低。为了获得最佳活性，必须在C-6位上强烈吸电子的取代基。当2-吡啶酮环被其他杂环如4-吡啶酮，嘧啶酮，哒嗪酮，吡嗪酮和1,4-丁烷磺胺取代时，活性得以维持。3-羟基官能团（---- 17a）的去除不会显着降低活性。从苯并二氢吡喃醇中除去水会导致苯并二氢吡喃酮的形成，这是已知最有效的降压药之一。各种取代基，尤其是杂环C-6取代基的影响，以4-（2-氧代-1-吡咯烷基）色满-3-醇系列进行了研究。铬醇在3-羟基处被短链酸酯化，保持其活性。色烯双键的环氧化也产生活性化合物。环氧化物22的重排产生3-酮化合物23和烯醇衍生物25。酮23a的还原产生顺式-苯并二氢吡喃醇7ab及其反式异构体7e。在自发性高血压大鼠中以1 mg / kg
• 4-Heterocyclyloxy-2H-1-benzopyran potassium channel activators
  作者：Rolf Bergmann、Volker Eiermann、Rolf Gericke

  DOI：10.1021/jm00172a013

  日期：1990.10

  The reaction of 2,4-dihydroxypyridine (2) with 3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (1) yielded the 4-[(1,2-dihydro-2-oxo-4-pyridyl)oxy] compound 3a, accompanied by small amounts of the isomeric 4-(1,2-dihydro-4-hydroxy-2-oxo-1-pyridyl) compound 4. This could also be prepared by hydrogenation of the benzyloxy derivative 5. Reaction of 3,6-pyridazinediol (10) with 1 (R = CN) gave the 4-[(1,6-dihydro-6-oxo-3-pyridazinyl)oxy] compound 11a, which in turn rearranged on heating with NaH in DMSO into the 4-(1,6-dihydro-3-hydroxy-6-oxo-1-pyridazinyl) compound 12. A series of 6-substituted analogues (R = CO2Me, CSNH2, NO2, Br) of 3a and 11a were synthesized. N-Alkylation led to compounds 14a-c (R = Me, Et, CHMe2). The 4-heterocyclyloxychromenes 9 and 16a were obtained by alkaline hydrolysis of their 3-camphorsulfonates. The racemic pyridazinyloxy compounds 11a and 14a could be resolved via their diastereomeric camphorsulfonates or camphanates. The differences between the 4-heterocyclyloxychromanols and the isomeric N-substituted compounds 4 and 12 were elucidated in the course of extensive NMR investigations. While in DMSO the former appeared to be conformationally flexible molecules the latter were rigid. All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats, using doses of 1 mg/kg. High and long lasting activities were found for the pyridyloxy compounds 3a and 3d, the pyridazinyloxy compound 11a, and its N-alkylation products, as well as for the 3S,4R-enantiomers 20a and 22a. (-)-(3S,4R)-3,4-Dihydro-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)oxy]-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (22a) was selected for further development.
• Pharmaceutically active benzopyran compounds
  申请人：BEECHAM GROUP PLC

  公开号：EP0076075B1

  公开（公告）日：1986-11-20