tert-butyl (2S,4S)-2-[[(1R,2S)-2-ethenyl-1-methoxycarbonylcyclopropyl]carbamoyl]-4-(4-nitrobenzoyl)oxypyrrolidine-1-carboxylate | 572922-90-8

• 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: tert-butyl (2S,4S)-2-[[(1R,2S)-2-ethenyl-1-methoxycarbonylcyclopropyl]carbamoyl]-4-(4-nitrobenzoyl)oxypyrrolidine-1-carboxylate
• CAS: 572922-90-8
• 化学式: C₂₄H₂₉N₃O₉
• 分子量: 503.509
• InChiKey: XQAGWUAHPDTAKR-RBBFAFJASA-N

物化性质

• 沸点：
  663.3±55.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,4S)-2-[[(1R,2S)-2-ethenyl-1-methoxycarbonylcyclopropyl]carbamoyl]-4-(4-nitrobenzoyl)oxypyrrolidine-1-carboxylate 在 dichloro(o-isporopoxyphenylmethylene)(triphenylphosphine)ruthenium(II) 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三环己基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 2.5h， 生成 (1S,4R,6S,7Z,14S,18S)-14-cyclopentyloxycarbonylamino-18-(4-nitro-benzoyloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Efficient Large-Scale Synthesis of BILN 2061, a Potent HCV Protease Inhibitor, by a Convergent Approach Based on Ring-Closing Metathesis

  摘要：

  A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce > 400 kg of cyclized product.

  DOI：

  10.1021/jo060285j
• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 偶氮二甲酸二异丙酯 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 生成 tert-butyl (2S,4S)-2-[[(1R,2S)-2-ethenyl-1-methoxycarbonylcyclopropyl]carbamoyl]-4-(4-nitrobenzoyl)oxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Efficient Large-Scale Synthesis of BILN 2061, a Potent HCV Protease Inhibitor, by a Convergent Approach Based on Ring-Closing Metathesis

  摘要：

  A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce > 400 kg of cyclized product.

  DOI：

  10.1021/jo060285j

文献信息

• [EN] HEPATITIS C INHIBITOR COMPOUNDS<br/>[FR] COMPOSES INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004103996A1

  公开（公告）日：2004-12-02

  Compounds of formula (I): wherein B, X, R3, L0, L1, L2, R2, R1 and RC are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  公式（I）的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如本文所述。这些化合物可用作丙型肝炎病毒NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• Macrocyclic peptides active against the hepatitis C virus
  申请人：Boehringer Ingelheim (Canada) Ltd.

  公开号：US20030224977A1

  公开（公告）日：2003-12-04

  Compounds of formula I: 1 wherein R 1 is hydroxy or NHSO 2 R 1A wherein R 1A is (C 1-8 )alkyl, (C 3-7 )cycloalkyl or {(C 1-6 )alkyl-(C 3-7 )cycloalkyl}, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O(C 1-6 )alkyl, amido, amino or phenyl, or R 1A is C 6 or C 10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C 1-6 )alkyl, O(C 1-6 )alkyl, amido, amino or phenyl; R 2 is (C 5-6 )cycloalkyl and R 3 is cyclopentyl; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.

  式I的化合物：其中R1是羟基或NHSO2R1A，其中R1A是（C1-8）烷基，（C3-7）环烷基或（C1-6）烷基-（C3-7）环烷基，这些都可以选择地被卤素，氰基，硝基，O（C1-6）烷基，酰胺基，氨基或苯基取代1到3次，或者R1A是C6或C10芳基，它可以选择地被卤素，氰基，硝基，（C1-6）烷基，O（C1-6）烷基，酰胺基，氨基或苯基取代1到3次；R2是（C5-6）环烷基，R3是环戊基；或其药用可接受的盐，用作HCV NS3蛋白酶的抑制剂。
• Hepatitis C inhibitor peptide analogs
  申请人：Bailey D. Murray

  公开号：US20060019905A1

  公开（公告）日：2006-01-26

  Compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , Y, n and m are as defined herein. The compounds are useful as inhibitors of HCV NS3 protease.

  式（I）的化合物：其中R1、R2、R3、R4、R5、Y、n和m的定义如本文所述。这些化合物可用作HCV NS3蛋白酶的抑制剂。
• Hepatitis C Inhibitor Compounds
  申请人：LLINAS-BRUNET Montse

  公开号：US20070243166A1

  公开（公告）日：2007-10-18

  Compounds of formula (I): wherein B, X, R 3 , L 0 , L 1 , L 2 , R 2 , R 1 and R C are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  式(I)的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如下。该化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• Hepatitis C Inhibitor Dipeptide Analogs
  申请人：BAILEY Murray D.

  公开号：US20090156822A1

  公开（公告）日：2009-06-18

  Compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , n and m are as defined herein. The compounds are useful as inhibitors of HCV NS3 protease.

  式(I)的化合物：其中R1、R2、R3、R4、n和m的定义如本文所述。该化合物可用作HCV NS3蛋白酶的抑制剂。