N-tert-Butyldecahydro-2-(2(R)-hydroxy-4-phenyl-3(S)phthalimidobutyl)-(4aS,8aS)-isoquinoline-3(S)-carboxamide | 136465-78-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-tert-Butyldecahydro-2-(2(R)-hydroxy-4-phenyl-3(S)phthalimidobutyl)-(4aS,8aS)-isoquinoline-3(S)-carboxamide
• 英文别名: N-tert.butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-phthalimidobutyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide；(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3S)-3-(1,3-dioxoisoindol-2-yl)-2-hydroxy-4-phenylbutyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide
• CAS: 136465-78-6
• 化学式: C₃₂H₄₁N₃O₄
• 分子量: 531.695
• InChiKey: RQMNITKWEGGNCN-VTSHJLIOSA-N

物化性质

• 沸点：
  730.6±60.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  90
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-tert-Butyldecahydro-2-(2(R)-hydroxy-4-phenyl-3(S)phthalimidobutyl)-(4aS,8aS)-isoquinoline-3(S)-carboxamide 在 palladium on activated charcoal N-乙基吗啉 、 盐酸 、 氢气 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 甲胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 97.0h， 生成 沙喹那韦
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026
• 作为产物：
  描述：

  [(2R,3S)-3-(1,3-dioxoisoindol-2-yl)-1-(oxan-2-yloxy)-4-phenylbutan-2-yl] methanesulfonate 在 potassium tert-butylate 、 对甲苯磺酸 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 N-tert-Butyldecahydro-2-(2(R)-hydroxy-4-phenyl-3(S)phthalimidobutyl)-(4aS,8aS)-isoquinoline-3(S)-carboxamide
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026

文献信息

• Alcohols
  申请人：Hoffmann-La Roche Inc.

  公开号：US05451678A1

  公开（公告）日：1995-09-19

  Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, --N(alkoxycarbonyl)-, --N(acyl)- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.

  化合物的式子为 ##STR1## 其中 R.sup.a 是 azido 或 phthalimido，R.sup.4 是烷基，环烷基，环烷基烷基，芳基或芳基烷基，R.sup.7 和 R.sup.8 在一起是三亚甲基或四亚甲基基团，该基团可选地被羟基，烷氧羰胺基或酰胺基取代，或其中一个 -CH.sub.2-基团被 -NH-, -N（烷氧羰基）-, -N（酰基）- 或 -S- 取代，或者带有融合的环烷基，芳香基或杂芳基环，并且 R.sup.9 是烷氧羰基，单烷基氨基甲酰基，单芳基氨基甲酰基，单芳基甲酰基或一个式子的基团 ##STR2## 其中 R.sup.10 和 R.sup.11 各自是烷基。同时还描述了制造这些化合物的过程。这些醇类化合物可用作中间体，例如在制造具有抗病毒活性的氨基酸衍生物时。
• Process for preparation of
  申请人：Hoffmann-La Roche Inc.

  公开号：US05641886A1

  公开（公告）日：1997-06-24

  The invention relates to a process for the preparation of N-tert.butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-phthalimidobutyl]-(4a S,8aS)-isoquinoline-3(S)-carboxamide of the formula ##STR1## as well as novel intermediates. The compound of formula I is a valuable intermediate for pharmacologically active compounds. The compound of formula I can be converted into pharmacologically active compounds which are suitable for the treatment of viral infections, such as those caused by HIV and other retroviruses.

  本发明涉及一种制备N-叔丁基-十氢-2-[2(R)-羟基-4-苯基-3(S)-邻苯二甲酰氨基丁基]-(4aS,8aS)-异喹啉-3(S)-羧酰胺的方法，其化学式为##STR1##以及新型中间体。式I化合物是制备药理活性化合物的有价值中间体。式I化合物可以转化为药理活性化合物，适用于治疗病毒感染，如HIV和其他逆转录病毒引起的感染。
• Oxirane intermediates for novel alcohols
  申请人：Hoffmann-La Roche Inc.

  公开号：US05508430A1

  公开（公告）日：1996-04-16

  Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, --N(alkoxycarbonyl)--, --N(acyl)-- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.

  本发明涉及一种新型醇，其化学式为##STR1##其中R.sup.a为偶氮基或邻苯二甲酰亚胺基，R.sup.4为烷基、环烷基、环烷基烷基、芳基或芳基烷基，R.sup.7和R.sup.8共同为三亚甲基或四亚甲基基团，该基团可以被羟基、烷氧羰基氨基或酰胺基取代，或其中一个--CH.sub.2--基团被--NH--、--N(烷氧羰基)--、--N(酰基)--或--S--取代，或者带有融合的环烷基、芳香基或杂芳基环，R.sup.9为烷氧羰基、单烷基氨基甲酰基、单芳基氨基甲酰基、单芳基甲酰基或式中R.sup.10和R.sup.11各自为烷基的基团。同时，本发明还涉及一种制备这些醇的方法。这些醇可用作中间体，例如在制备具有抗病毒活性的氨基酸衍生物时。
• Verfahren zur Herstellung eines N-tert.Butylisochinolin-3-carboxamid Derivates und Zwischenprodukte in diesem Verfahren
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0634410A1

  公开（公告）日：1995-01-18

  Verfahren zur Herstellung des N-tert.Butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-phthalimidobutyl]-(4aS,8aS)-isochinolin-3(S)-carboxamids der Formel durch reduktive Aminierung des dem Alkohol I entsprechenden α-Hydroxyaldehyds; Verfahren zur Herstellung von Vorprodukten zu diesem α-Hydroxyaldehyd, sowie neue in diesen Verfahren vorkommende Zwischenprodukte.

  一种制备 N-叔丁基-十氢-2-[2(R)-羟基-4-苯基-3(S)-邻苯二甲酰亚胺丁基]-(4aS,8aS)-异喹啉-3(S)-甲酰胺的工艺，其式如下 通过与醇 I 相对应的α-羟基醛的还原胺化反应；制备这种α-羟基醛的前体的工艺，以及在这些工艺中出现的新的中间体。
• Goehring, Wolfgang; Gokhale, Surendra; Hilpert, Hans, Chimia, 1996, vol. 50, # 11, p. 532 - 537
  作者：Goehring, Wolfgang、Gokhale, Surendra、Hilpert, Hans、Roessler, Felix、Schlageter, Markus、Vogt, Peter

  DOI：——

  日期：——