2H-1-苯并吡喃-4-醇,3-溴-6-乙基-3,4-二氢-2,2-二甲基-,反- | 117610-34-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 2H-1-苯并吡喃-4-醇,3-溴-6-乙基-3,4-二氢-2,2-二甲基-,反-
• 英文名称: (3R,4S)-3-bromo-6-ethyl-2,2-dimethyl-3,4-dihydrochromen-4-ol
• CAS: 117610-34-1
• 化学式: C₁₃H₁₇BrO₂
• 分子量: 285.181
• InChiKey: ADECBWLBAHNGLU-NWDGAFQWSA-N

物化性质

• 沸点：
  356.1±42.0 °C(Predicted)
• 密度：
  1.358±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2H-1-苯并吡喃-4-醇,3-溴-6-乙基-3,4-二氢-2,2-二甲基-,反- 在 氢氧化钾 、 sodium hydride 作用下， 以 乙醚 、 二甲基亚砜 为溶剂， 生成 1-[(3R,4S)-6-ethyl-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]pyrrolidin-2-one
  参考文献：
  名称：

  Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans

  摘要：

  The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl.

  DOI：

  10.1021/jm00173a018
• 作为产物：
  描述：

  4-乙基苯酚 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 水 、 苄基三甲基氢氧化铵 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 邻二氯苯 为溶剂， 反应 1.0h， 生成 2H-1-苯并吡喃-4-醇,3-溴-6-乙基-3,4-二氢-2,2-二甲基-,反-
  参考文献：
  名称：

  Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans

  摘要：

  The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl.

  DOI：

  10.1021/jm00173a018

文献信息

• Pharmacologically active benzopyranes
  申请人：BEECHAM GROUP PLC

  公开号：EP0250077A2

  公开（公告）日：1987-12-23

  Compounds of formula (I) and pharmaceutically accetable salts thereof: wherein: Y is N or (when R3 is hydroxy, C1-6 alkoxy or C1-7 acyloxy) CH; one of R1 and R2 is hydrogen or C1-4 alkyl and the other is C1-4 alkyl or R1 and R2 together are C2-s-polymethylene; R3 is hydrogen, hydroxy, C1-6 alkoxy or C1-7 acyloxy; R4 is a C3-8 cycloalkyl group or a C1-6 alkyl group optionally substituted by a group R7 which is hydroxy, C1-6 alkoxy, amino optionally substituted by one or two C1-6 alkyl groups; C1-7 alkanoylamino, C3-8 cycloalkyloxy, C3-8 cycloalkylamino, or 1,3-dioxo-2-isoindoline; when Y is N, R5 is hydrogen, C1-6 alkyl optionally substituted by halogen, hydroxy, C1-6 alkoxy, C1-6 alkoxycarbonyl, carboxy or amino optionally substituted by one or two independent C1-6 alkyl groups, or C2-6 alkenyl, amino optionally substituted by a C1-6 alkyl, C3-a cycloalkyl or C1-6 alkenyl group or by a C1-6 alkanoyl group optionally substituted by up to three halo atoms, by a phenyl group optionally substituted by C1-6 alkyl, C1-6 alkoxy or halogen, or aryl or heteroaryl, either being optionally substituted by one or more groups or atoms selected from the class of C1-6 alkyl, C1-6 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, C1-12 carboxylic acyl, or amino or aminocarbonyl optionally substituted by one or two C1-6 alkyl groups and R6 is hydrogen or C1-6 alkyl, or R5 and R6 together are -CH2-(CH2)n-Z-(CH2)m- wherein m and n are 0 to 2 such that m + n is 1 or 2 and Z is CH2, O, S or NR wherein R is hydrogen, C1-9 alkyl, C2-7 alkanoyl, phenyl C1-4-alkyl, naphthylcarbonyl, phenylcarbonyl or benzyl-carbonyl optionally substituted in the phenyl or naphthyl ring by one or two of C1-6 alkyl, C1-6 alkoxy or halogen; mono- or bi-cyclic- heteroarylcarbonyl; when Y is CH, R5 is NR8R9 wherein R8 and R9 are independently C1-6 alkyl, R8 is hydrogen and R9 is C1-6 alkyl or R8 and R9 together are C4-5 polymethylene; or R6 and R8 together are -(CH2)p- wherein p is 2 or 3, and R9 is hydrogen or C1-6 alkyl; or R5 is CH2R10 wherein R10 is hydrogen or C1-5 alkyl; or R6 and R10 are -(CH2)q- wherein q is 2 or 3; X is oxygen or sulphur; or R5, R6, X and Y (when N) together are tetrahydroisoquinolinone ortetrahydroisoquinolinthione, optionally substituted in the phenyl ring as defined for R above; the nitrogen-containing group is in the 4-position being trans to the R3 group when R3 is hydroxy, C1-6 alkoxy or C1-7 acyloxy; having K+ channel activator activity, processes for their preparation and their use as pharmaceuticals.

  式 (I) 的化合物及其可药用盐： 其中 Y 是 N 或（当 R3 是羟基、C1-6 烷氧基或 C1-7 乙酰氧基时）CH； R1 和 R2 中的一个是氢或 C1-4 烷基，另一个是 C1-4 烷基，或 R1 和 R2 合在一起是 C2-s 聚亚甲基； R3 是氢、羟基、C1-6 烷氧基或 C1-7 丙烯酸氧基； R4 是 C3-8 环烷基或任选被一个基团 R7 取代的 C1-6 烷基，该基团是羟基、C1-6 烷氧基、任选被一个或两个 C1-6 烷基取代的氨基、C1-7 烷酰氨基、C3-8 环烷氧基、C3-8 环烷基氨基或 1,3-二氧代-2-异吲哚啉； 当 Y 是 N 时，R5 是氢、任选被卤素、羟基、C1-6 烷氧基、C1-6 烷氧羰基、羧基或任选被一个或两个独立 C1-6 烷基取代的氨基取代的 C1-6 烷基，或 C2-6 烯基、任选被 C1-6 烷基取代的氨基、C3-a环烷基或C1-6烯基，或被最多三个卤原子任选取代的C1-6烷酰基，或被C1-6烷基、C1-6烷氧基或卤素任选取代的苯基，或芳基或杂芳基，其中任一芳基或杂芳基被一个或多个选自C1-6烷基类的基团或原子任选取代、C1-6烷氧基、羟基、卤素、三氟甲基、硝基、氰基、C1-12 羧酰基或氨基或氨基羰基中任选被一个或两个 C1-6 烷基取代，且 R6 为氢或 C1-6 烷基，或 R5 和 R6 合在一起为-CH2-(CH2)n-Z-(CH2)m-，其中 m 和 n 为 0 至 2，使得 m + n 为 1 或 2，且 Z 为 CH2、O、S 或 NR，其中 R 是氢、C1-9 烷基、C2-7 烷酰基、苯基 C1-4-烷基、萘基羰基、苯基羰基或苄基羰基，可选择在苯基或萘基环上被一个或两个 C1-6 烷基、C1-6 烷氧基或卤素取代；单环或双环杂芳基羰基； 当 Y 是 CH 时，R5 是 NR8R9，其中 R8 和 R9 独立地是 C1-6 烷基，R8 是氢，R9 是 C1-6 烷基，或 R8 和 R9 一起是 C4-5 聚亚甲基；或 R6 和 R8 一起是-(CH2)p-，其中 p 是 2 或 3，R9 是氢或 C1-6 烷基；或 R5 是 CH2R10，其中 R10 是氢或 C1-5 烷基；或 R6 和 R10 是-(CH2)q-，其中 q 是 2 或 3； X 是氧或硫；或 R5、R6、X 和 Y（当为 N 时）一起是四氢异喹啉酮或四氢异喹啉乙硫酮，如上文对 R 所定义，可选择被取代的苯基环； 当 R3 为羟基、C1-6 烷氧基或 C1-7 乙酰氧基时，含氮基团位于反式至 R3 基团的 4 位；具有 K+通道激活剂活性，其制备工艺及其作为药物的用途。
• An unusual base-mediated ring contraction reaction of benzopyrans to benzofurans
  作者：Derek R. Buckle、Andrew Faller、Ivan L. Pinto、David G. Smith

  DOI：10.1016/s0040-4039(00)91873-2

  日期：1992.2

  The reaction of electron deficient pyrroles and pyrazoles with trans 3-bromo-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-ol under basic conditions results in the formation of 2-isopropylbenzofurans by a mechanism which appears to be dependent on the rate of the competitive dehydration reaction leading to the corresponding benzopyrans.
• US4943582A
  申请人：——

  公开号：US4943582A

  公开（公告）日：1990-07-24
• US5075460A
  申请人：——

  公开号：US5075460A

  公开（公告）日：1991-12-24
• US5210234A
  申请人：——

  公开号：US5210234A

  公开（公告）日：1993-05-11