2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)ethyl 4-methylbenzenesulfonate | 104265-58-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)ethyl 4-methylbenzenesulfonate
• 英文别名: toluene-4-sulfonic acid 2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl ester；(1S,2S)-6-fluoro-1-isopropyl-2-[2-(4-toluenesulfonyloxy)ethyl]-1,2,3,4-tetrahydronaphthalene-2-ol；2-[(1S,2S)-6-fluoro-2-hydroxy-1-propan-2-yl-3,4-dihydro-1H-naphthalen-2-yl]ethyl 4-methylbenzenesulfonate
• CAS: 104265-58-9
• 化学式: C₂₂H₂₇FO₄S
• 分子量: 406.518
• InChiKey: ROTGKNXENPLVHL-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)ethyl 4-methylbenzenesulfonate 在 硼烷四氢呋喃络合物 、 水 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 7.8h， 生成 (1S,2S)-6-fluoro-2-[2-({3-[(2-fluoro-ethyl)-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-amino]-propyl}-methyl-amino)-ethyl]-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-ol
  参考文献：
  名称：

  TETRAHYDRONAPHTHALENE COMPOUNDS

  摘要：

  这项发明涉及到式（I）化合物，其中R1、R2、R3、R4、R5、m和n如描述中定义，并且涉及到这些化合物的药用盐。这些化合物可用作钙通道阻滞剂。

  公开号：

  US20110207815A1
• 作为产物：
  描述：

  (1S,2S)-6-fluoro-2-(2-hydroxyethyl)-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-ol 、 对甲苯磺酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 甲苯 为溶剂， 生成 2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  TETRAHYDRONAPHTHALENE COMPOUNDS

  摘要：

  这项发明涉及到式（I）化合物，其中R1、R2、R3、R4、R5、m和n如描述中定义，并且涉及到这些化合物的药用盐。这些化合物可用作钙通道阻滞剂。

  公开号：

  US20110207815A1

文献信息

• Tetrahydronaphthalene derivatives as calcium antagonists
  申请人：Hoffmann-La Roche Inc.

  公开号：US04808605A1

  公开（公告）日：1989-02-28

  Compounds of the formula ##STR1## wherein R is lower-alkyl, R.sup.1 is halogen, R.sup.2 is C.sub.1 -C.sub.12 -alkyl, R.sup.3 is hydroxy, lower-alkoxy, lower-alkyl-carbonyloxy, lower-alkoxy-lower-alkylcarbonoyloxy, lower-alkylaminocarbonyloxy, arylaminocarbonyloxy or aryl-lower alkylaminocarbonyloxy, X is C.sub.1 -C.sub.18 -alkylene which optionally can be interrupted by 1,4-phenylene or interrupted or lengthened by 1,4-cyclohexylene, A is di- or tri-substituted 2-imidazolyl attached via an ethylene group or a substituted or unsubstituted heterocycle selected from the group consisting of benzimidazolyl, benzimidazolonyl, imidazo[4,5-c]pyridinyl, imidazo[4,5-c]pyridinonyl, benzthiazolyl, benzodiazepine-2,5-dion-1-yl and pyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-dion-10-yl and n is the number 0 or 1, in the form of racemates and optical antipodes, as well as N-oxides and pharmaceutically usable acid addition salts thereof. The compounds of formual I have a pronounced calcium-antagonistic and anti-arrhythmic activity and can accordingly be used as medicaments, especially for the control or prevention of angina pectoris, ischaemia, arrhythmias, high blood pressure and cardiac insufficiency.

  式为##STR1##的化合物，其中R是低碳基，R.sup.1是卤素，R.sup.2是C.sub.1-C.sub.12-烷基，R.sup.3是羟基，低碳氧基，低碳基羧酸酯，低碳氧基-低碳基羧酸酯，低碳基氨基羧酸酯，芳基氨基羧酸酯或芳基-低碳基氨基羧酸酯，X是C.sub.1-C.sub.18-烷基，可以选择性地被1,4-苯基撑开或被1,4-环己基打断或延长，A是二或三取代的2-咪唑基，通过乙烯基或选择自苯并咪唑基，苯并咪唑酰基，咪唑[4,5-c]吡啶基，咪唑[4,5-c]吡啶酰基，苯并噻唑基，苯并二氮杂环-2,5-二酮-1-基和吡咯[2,1-c]-[1,4]苯并二氮杂环-5,11-二酮-10-基的取代或未取代的杂环团组成，n是数字0或1，以外消旋体和光学对映体的形式存在，以及其N-氧化物和药用酸盐。公式I的化合物具有显著的钙拮抗和抗心律失常活性，因此可以用作药物，特别是用于控制或预防心绞痛，缺血，心律失常，高血压和心力衰竭。
• Preparation of mibefradil via an acetamide anion
  申请人：Roche Colorado Corporation

  公开号：US05808088A1

  公开（公告）日：1998-09-15

  A method of preparing 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino)}ethyl!-6-fluoro-1-isopr opyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting 6-fluoro-1-isopropyl-3,4-dihydro-1H-naphthalen-2-one with the dianion of N-\x9b3-(1H-benzimidazol-2-yl)propyl!-N-methylacetamide to form N-\x9b3-(1H-benzimidazol-2-yl)propyl!-2-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3 ,4-tetrahydronaphthalen-2-yl)-N-methylacetamide, reducing this to 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-ol, and treating the 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid. The invention is particularly applicable to the preparation of mibefradil, (lS,2S)-2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro- 1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, and its dihydrochloride salt. N-\x9b3-(1H-Benzimidazol-2-yl)propyl!-N-methylacetamide, and the acetic acid solvate of 2-\x9b2- \x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopropyl-1 ,2,3,4-tetrahydronaphthalen-2-ol dioxalate, are new.

  一种制备2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基)}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-基甲氧基乙酸酯的方法包括将6-氟-1-异丙基-3,4-二氢-1H-萘-2-酮与N-\x9b3-(1H-苯并咪唑-2-基)丙基!-N-甲基乙酰胺的二阴离子接触以形成N-\x9b3-(1H-苯并咪唑-2-基)丙基!-2-(6-氟-2-羟基-1-异丙基-1,2,3,4-四氢萘-2-基)-N-甲基乙酰胺，将其还原为2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-醇，然后用甲氧基乙酸或甲氧基乙酸的活性衍生物处理2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-醇。该发明特别适用于制备米贝伐利（lS，2S）-2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-基甲氧基乙酸酯及其双盐酸盐。N-\x9b3-(1H-苯并咪唑-2-基)丙基!-N-甲基乙酰胺和2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-醇草酸二乙酸盐的乙酸溶剂化物是新的。
• Preparation of mibefradil via an acetonitrile anion
  申请人：Roche Colorado Corporation

  公开号：US05811557A1

  公开（公告）日：1998-09-22

  A method of preparing 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting 6-fluoro-1-isopropyl-3,4-dihydro-1H-naphthalen-2-one with the anion of acetonitrile in an aprotic polar solvent; contacting \x9b3-(1H-benzitidazol-2-yl)propyl!methylamine with the thus-formed (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetonit rile in the presence of hydrogen and a hydrogenation catalyst, followed by contacting the thus-formed 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid. The invention is particularly applicable to the preparation of mibefradil, (1S,2S)-2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro- 1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, and its dihydrochloride salt. (6-Fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl) acetonitrile is new.

  一种制备2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-基甲氧基乙酸酯的方法包括将6-氟-1-异丙基-3,4-二氢-1H-萘-2-酮与乙腈的阴离子在无水极性溶剂中接触;在氢气和氢化催化剂的存在下将\x9b3-(1H-苯并咪唑-2-基)丙基!甲基胺与由此形成的(6-氟-2-羟基-1-异丙基-1,2,3,4-四氢萘-2-基)乙腈接触，然后将形成的2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-醇与甲氧基乙酸或甲氧基乙酸的活性衍生物接触。该发明特别适用于制备米贝拉地尔，(1S,2S)-2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-基甲氧基乙酸酯及其二盐酸盐。 (6-氟-2-羟基-1-异丙基-1,2,3,4-四氢萘-2-基)乙腈是新的。
• Preparation of mibefradil via a naphthalenylacetic acid
  申请人：Roche Colorado Corporation

  公开号：US05811556A1

  公开（公告）日：1998-09-22

  A method of preparing 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid or an activated derivative of (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid with \x9b3-(1H-benzimidazol-2-yl)propyl!methylamine to form N-\x9b3-(1H-benzimidazol-2-yl) propyl!-2-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3 ,4-tetrahydronaphthalen-2- yl)-N-methylacetamide, reducing this to 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1, 2,3,4-tetrahydronaphthalen-2-ol, and treating the 2-\x9b2-\x9b3-(1H-benzimidazol-2-yl) propyl!-methylamino}ethyl!-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthal en-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid. The invention is particularly applicable to the preparation of mibefradil, (1S,2S)-2-\x9b2-\x9b3-(1H-benzimidazol-2-yl)propyl!methylamino}-ethyl!-6-fluoro -1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, and its dihydrochloride salt. N-\x9b3-(1H-benzimidazol-2yl)propyl!-2-(6-fluoro-2-hydroxy-1-isopropyl-1, 2,3,4-tetrahydronaphthalen-2-yl)-N-methylacetamide is new.

  一种制备2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-基甲氧基乙酸酯的方法，包括将(6-氟-2-羟基-1-异丙基-1,2,3,4-四氢萘-2-基)乙酸或其活化衍生物与\x9b3-(1H-苯并咪唑-2-基)丙基!甲基胺接触，形成N-\x9b3-(1H-苯并咪唑-2-基)丙基!-2-(6-氟-2-羟基-1-异丙基-1,2,3,4-四氢萘-2-基)-N-甲基乙酰胺，将其还原为2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-醇，并用甲氧基乙酸或其活化衍生物处理2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!-甲基氨基}乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-醇。该发明特别适用于制备米贝拉地尔、(1S,2S)-2-\x9b2-\x9b3-(1H-苯并咪唑-2-基)丙基!甲基氨基}-乙基!-6-氟-1-异丙基-1,2,3,4-四氢萘-2-基甲氧基乙酸酯及其二盐酸盐。N-\x9b3-(1H-苯并咪唑-2-基)丙基!-2-(6-氟-2-羟基-1-异丙基-1,2,3,4-四氢萘-2-基)-N-甲基乙酰胺是新的。
• Tetrahydronaphthalene compounds
  申请人：Hilpert Kurt

  公开号：US08436205B2

  公开（公告）日：2013-05-07

  The invention relates to compounds of Formula (I) wherein R1, R2, R3, R4, R5, m and n are as defined in the description, and to pharmaceutically acceptable salts of such compounds. These compounds are useful as calcium channel blockers.

  本发明涉及公式（I）中的化合物，其中R1、R2、R3、R4、R5、m和n如描述中所定义，并且涉及这些化合物的药学上可接受的盐。这些化合物可用作钙通道阻滞剂。