{[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 2-(2-oxo-1-pyrrolidinyl)ethyl carbonate | 1206168-23-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: {[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 2-(2-oxo-1-pyrrolidinyl)ethyl carbonate
• 英文别名: [(3R,6S)-12-[(2,4-difluorophenyl)methylcarbamoyl]-6-methyl-8,11-dioxo-4-oxa-1,7-diazatricyclo[7.4.0.03,7]trideca-9,12-dien-10-yl]oxymethyl 2-(2-oxopyrrolidin-1-yl)ethyl carbonate
• CAS: 1206168-23-1
• 化学式: C₂₇H₂₈F₂N₄O₉
• 分子量: 590.538
• InChiKey: MUICAICQTIOAPI-YCRPNKLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  144
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  {[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 4-nitrophenyl carbonate 、 N-羟乙基-2-吡咯烷酮 、 三乙胺 在 4-二甲氨基吡啶 {[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 2-(2-oxo-1-pyrrolidinyl)ethyl carbonate 、 silica 作用下， 生成 {[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 2-(2-oxo-1-pyrrolidinyl)ethyl carbonate
  参考文献：
  名称：

  1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylic acid of the formula P-6 and/or methyl 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate of the formula P-7

  摘要：

  这些化合物是在制备治疗病毒感染，特别是HIV感染的治疗剂时的中间体。这些化合物是P-6式的1-(2,3-二羟基丙基)-4-氧代-3-[(苯甲基)氧基]-1,4-二氢-2-吡啶羧酸和/或P-7式的甲酯基1-(2,3-二羟基丙基)-4-氧代-3-[(苯甲基)氧基]-1,4-二氢-2-吡啶羧酸酯。

  公开号：

  US08765965B2
• 作为试剂：
  描述：

  {[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 4-nitrophenyl carbonate 、 N-羟乙基-2-吡咯烷酮 、 三乙胺 在 4-二甲氨基吡啶 {[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 2-(2-oxo-1-pyrrolidinyl)ethyl carbonate 、 silica 作用下， 生成 {[(3S,11aR)-8-({[(2,4-difluorophenyl)methyl]amino}carbonyl)-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazin-6-yl]oxy}methyl 2-(2-oxo-1-pyrrolidinyl)ethyl carbonate
  参考文献：
  名称：

  CHEMICAL COMPOUNDS

  摘要：

  本发明涉及化合物，它们是HIV整合酶抑制剂的前体药物，因此在输送用于抑制HIV复制的化合物、预防和/或治疗HIV感染以及治疗AIDS和/或ARC方面非常有用。

  公开号：

  US20110183940A1

文献信息

• Methyl 3-(benzyloxy)-1-(2,2-dihydroxyethyl)-4-oxo-1,4-dihydropyridine-2-carboxylate and processes for the preparation thereof
  申请人：Johns Brian Alvin

  公开号：US08580967B2

  公开（公告）日：2013-11-12

  The present invention features compounds that are prodrugs of HIV integrase inhibitors and therefore are useful in the delivery of compounds for the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC. For example, the present invention includes methyl 3-(benzyloxy)-1-(2,2-dihydroxyethyl)-4-oxo-1,4-dihydropyridine-2 -carboxylate of the formula P-8: and processes for the preparation thereof.

  本发明涉及HIV整合酶抑制剂的前药化合物，因此可用于传递化合物以抑制HIV复制，预防和/或治疗HIV感染，并用于治疗艾滋病和/或ARC。例如，本发明包括式P-8的甲基3-(苄氧基)-1-(2,2-二羟乙基)-4-氧代-1,4-二氢吡啶-2-羧酸甲酯及其制备方法。
• 2-(2-hydroxy-2-phenylethyl)-3-[(phenylmethyl)oxy]-4H-pyran-4-one of the formula P-3 and/or 2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-Pyran-4-one of the formula P-4
  申请人：Shionogi & Co., Ltd.

  公开号：US08981129B2

  公开（公告）日：2015-03-17

  The compounds are intermediates in the preparation of therapeutic agents useful in the treatment of viral infections, particularly HIV infection. The compounds are 2-(2-hydroxy-2-phenylethyl)-3-[(phenylmethyl)oxy]-4H-pyran-4-one of the formula P-3 and/or 2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-pyran-4-one of the formula P-4.

  这些化合物是在制备治疗病毒感染，特别是HIV感染的治疗剂中使用的中间体。这些化合物是P-3式的2-(2-羟基-2-苯乙基)-3-[(苯甲基)氧基]-4H-吡喃-4-酮和/或P-4式的2-[(E)-2-苯乙烯基]-3-[(苯甲基)氧基]-4H-吡喃-4-酮。
• (3S,11aR)-6-[(PHENYLMETHYL)OXY]-3-METHYL-2,3,11,11a-TETRAHYDROOXAZOLO[3,2-a]PYRIDO[1,2-d]PYRAZINE-5,7-DIONE OF THE FORMULA P-9 AND/OR (3S,11aR)-6-[(PHENYLMETHYL)OXY]-8-BROMO-3-METHYL-2,3,11,11a-TETRAHYDROOXAZOLO[3,2-a]PYRIDO[1,2-d]PYRAZINE-5,7-DIONE OF THE FORMULA P-10
  申请人：Shionogi & Co., Ltd.

  公开号：US20150183803A1

  公开（公告）日：2015-07-02

  The present invention features compounds that are prodrugs of HIV integrase inhibitors and therefore are useful in the delivery of compounds for the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

  本发明涉及一种HIV整合酶抑制剂的前药化合物，因此在传递用于抑制HIV复制的化合物、预防和/或治疗HIV感染以及治疗AIDS和/或ARC方面非常有用。
• 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid
  申请人：ViiV Healthcare Company

  公开号：US08940912B2

  公开（公告）日：2015-01-27

  The present invention features a process for the preparation of 4-oxo-3-[(phenylmethyl)oxy]-4-H-pyran-2-carboxylic acid, an intermediate useful in the synthesis of HIV integrase inhibitors. The process involves (a) treating a compound of formula P-2 with lithium bis(trimethylsilyl)amide and benzaldehyde to form a compound of formula P-3, (b) treating the compound of formula P-3 with triethylamine and methanesulfonyl chloride followed by N-methyl-2-pyrrolidone and 1,8-diazabicyclo[5.4.0]undec-7-ene to form a compound of formula P-4, and (c) treating the compound of formula P-4 with RuCl3 and NaIO4 to form the compound of formula P-5.

  本发明涉及一种制备4-氧代-3-[(苯甲基)氧基]-4H-吡喃-2-羧酸的方法，该中间体在合成HIV整合酶抑制剂中有用。该方法包括(a)用锂双(三甲基硅基)胺和苯甲醛处理P-2式化合物以形成P-3式化合物，(b)用三乙胺和甲磺酰氯处理P-3式化合物，然后用N-甲基-2-吡咯烷酮和1,8-二氮杂双环[5.4.0]十一烯处理以形成P-4式化合物，(c)用RuCl3和NaIO4处理P-4式化合物以形成P-5式化合物。
• Chemical compounds as synthetic intermediates
  申请人：VIIV Healthcare Company

  公开号：EP2660239A1

  公开（公告）日：2013-11-06

  Herein described are compounds that are prodrugs of HIV integrase inhibitors and therefore are useful in the delivery of compounds for the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC. The present invention features synthetic intermediates and their prepartion.

  本发明所描述的化合物是 HIV 整合酶抑制剂的原药，因此可用于递送抑制 HIV 复制、预防和/或治疗 HIV 感染以及治疗 AIDS 和/或 ARC 的化合物。本发明的特点是合成中间体及其制备。