4-(tert-butyloxycarbonylamino)phenyl isocyanide | 202745-13-9

• 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: 4-(tert-butyloxycarbonylamino)phenyl isocyanide
• 英文别名: N-[(tert-butoxy)carbonyl]-4-isocyanoaniline；tert-butyl N-(4-isocyanophenyl)carbamate
• CAS: 202745-13-9
• 化学式: C₁₂H₁₄N₂O₂
• 分子量: 218.255
• InChiKey: QWUJGOIESPJIMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(tert-butyloxycarbonylamino)phenyl isocyanide 在 六甲基二锡 、 三氟乙酸 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 8.0h， 生成 10-氨基喜树碱
  参考文献：
  名称：

  A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles

  摘要：

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.

  DOI：

  10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f
• 作为产物：
  描述：

  tert-butyl [4-(formylamino)phenyl]carbamate 在 四溴化碳 、 三乙胺 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以58%的产率得到4-(tert-butyloxycarbonylamino)phenyl isocyanide
  参考文献：
  名称：

  A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles

  摘要：

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.

  DOI：

  10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f

文献信息

• Total Synthesis of Luotonin and a Small Library of AB-Ring SubstitutedAnalogues by Cascade Radical Annulation of Isonitriles
  作者：Dennis P. Curran、Raghuraman Tangirala、Smitha Antony、Keli Agama、Yves Pommier

  DOI：10.1055/s-2005-918923

  日期：——

  A four-step total synthesis of luotonin is deployed to make a small library of AB-ring substituted analogues. These analogues show weak activity in a standard topoisomerase I mediated DNA cleavage assay.

  采用四步骤全合成法，制备了一批AB环替换类似物的小型库。这些类似物在标准拓扑异构酶I介导的DNA切割实验中表现出较弱的活性。
• 5-<i>Endo</i> Trig Oxidative Radical Cyclizations of Ugi-3CR Products toward 1,4-Imidazolidinones
  作者：Kevin Schofield、Christopher Foley、Christopher Hulme

  DOI：10.1021/acs.orglett.0c03785

  日期：2021.1.1

  A 5-endo trig oxidative radical cyclization of benzylamine-derived Ugi three-component reaction products rapidly affords imidazolidinones with three diversity elements. This adaptation of our previously described multicomponent reaction–oxidation methodology further showcases manipulation of the diversity elements in multicomponent reaction products via oxidative radical cyclizations, which generates

  苄胺衍生的Ugi三组分反应产物的5-内酯Trig氧化自由基环化迅速提供具有三种多样性元素的咪唑烷酮。我们先前描述的多组分反应-氧化方法的这种改进进一步展示了通过氧化自由基环化对多组分反应产物中多样性元素的操纵，从而生成了高度修饰的特权杂环。
• [EN] CAMPTOTHECIN ANALOGS AND METHODS OF PREPARATION THEREOF<br/>[FR] ANALOGUES DE LA CAMPTOTHECINE ET PROCEDE DE PREPARATION ASSOCIES
  申请人：UNIV PITTSBURGH

  公开号：WO2000061146A1

  公开（公告）日：2000-10-19

  A compound has formula (1) in racemic form, enantiomerically enriched form or enantiomerically pure form. R6 is preferably -Si(R8R9R1O) or -(R?7)Si(R8R9R10¿), wherein R7 is an alkylene group, an alkenylene group, or an alkynylene group; and R?8, R9 and R10¿ are independently a C¿1-10? alkyl group, a C?2-10¿ alkenyl group, a C2-10 alkynyl group, an aryl group or a -(CH¿2)NR?11 group, wherein N is an integer within the range of 1 through 10 and R11 is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, -SRc or a nitro group. R1-R4 can be broadly substituted. R5 is preferably a C¿1-10? alkyl group, an alkenyl group, an alkynyl group, or a benzyl group. R?13¿ is preferably H, F or -CH¿3. R?16 is -C(O)Rf or H. The E-ring (the lactone ring) may be opened. A method of synthesis of compound (1) and intermediates in the synthesis thereof are provided.

  该化合物的式子为(1)，可以是外消旋型，对映富集型或对映纯型。其中R6首选为-Si(R8R9R1O)或-(R7)Si(R8R9R10)，其中R7为烷基、烯基或炔基；而R8、R9和R10则分别是C1-10烷基、C2-10烯基、C2-10炔基、芳基或-(CH2)NR11，其中N为1至10的整数，而R11为羟基、烷氧基、氨基、烷基氨基、二烷基氨基、卤素原子、氰基、-SRc或硝基。R1-R4可以广泛取代。R5首选为C1-10烷基、C2-10烯基、C2-10炔基或苄基。R13首选为H、F或-CH3。R16为-C(O)Rf或H。E环（内酯环）可以打开。提供了化合物（1）的合成方法和合成中间体。
• [EN] CAMPTOTHECIN ANALOGS AND METHODS OF PREPARATION THEREOF<br/>[FR] ANALOGUES DE CAMPTOTHECINE ET METHODES DE PREPARATION
  申请人：UNIV PITTSBURGH

  公开号：WO2000035924A1

  公开（公告）日：2000-06-22

  A compound and a method of synthesizing a compound having general formula (1): wherein R?1 and R2¿ are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxy group, an aryloxy group, an acyloxy group, -OC(O)ORd, wherein Rd is an alkyl group, a carbamoyloxy group, a halogen, a hydroxy group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, -SRc, wherein Rc is hydrogen, an acyl group, an alkyl group, or an aryl group, or R?1 and R2¿ together form a group of the formula -O(CH¿2?)nO- wherein n represents the integer 1 or 2; R?3¿ is H, F, a halogen atom, a nitro group, an amino group, a hydroxy group, or a cyano group; or R?2 and R3¿ together form a group of the formula -O(CH¿2?)n O- wherein n represents the integer 1 or 2; R?4¿ is H, a trialkylsilyl group, F, a C¿1-3? alkyl group, a C2-3 alkenyl group, a C2-3 alkynyl group, or a C1-3 alkoxy group; R?5¿ is a C¿1-10? alkyl group, an allyl group, a benzyl group or a propargyl group; and R?6, R7 and R8¿ are independently a C¿1-10? alkyl group, a C2-10 alkenyl group, a C2-10 alkynyl group, an aryl group or a -(CH2)NR?9¿ group, wherein N is an integer within the range of 1 through 10 and R9 is a hydroxy group, alkoxy group, an amino group, alkylamino group, a dialkylamino group, a halogen atom, a cyano group or a nitro group; and R11 is an alkylene group or an alkenylene group, and pharmaceutically acceptable salts thereof.

  一种化合物及其合成方法，其具有通式（1）： 其中R1和R2独立且相同或不同，可以是氢、烷基、烯基、苄基、炔基、烷氧基、芳氧基、酰氧基、-OC（O）ORd（其中Rd为烷基、氨基甲酰氧基、卤素、羟基、硝基、氰基、叠氮基、甲酰基、肼基、酰基、氨基、-SRc（其中Rc为氢、酰基、烷基或芳基），或R1和R2组成式为-O（CH2）nO-的基团，其中n表示整数1或2；R3为氢、氟、卤素原子、硝基、氨基、羟基或氰基；或R2和R3组成式为-O（ ）nO-的基团，其中n表示整数1或2；R4为氢、三烷基硅基、氟、C1-3烷基、C2-3烯基、C2-3炔基或C1-3烷氧基；R5为C1-10烷基、烯丙基、苄基或丙炔基；R6、R7和R8独立地为C1-10烷基、C2-10烯基、C2-10炔基、芳基或-( )NR9（其中N为1至10的整数，R9为羟基、烷氧基、氨基、烷基氨基、二烷基氨基、卤素原子、氰基或硝基）；R11为烷基或烯基，以及其药物可接受的盐。
• Camptothecin analogs and methods of preparation thereof
  申请人：——

  公开号：US20010003779A1

  公开（公告）日：2001-06-14

  A method of synthesizing a compound having the formula 1 via a cascade radical 4+1 annulation includes the step wherein the precursor 2 is reacted with an arylisonitrile having the formula 3 wherein X is a radical precursor such as Cl, Br or I. R 6 is preferably —Si(R 8 R 9 R 10 ) or —(R 7 )Si(R 8 R 9 R 10 ), wherein R 7 is an alkylene group, an alkenylene group, or an alkynylene group; and R 8 , R 9 and R 10 are independently a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, an aryl group or a —(CH 2 ) N R 11 group, wherein N is an integer within the range of 1 through 10 and R 11 is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group, —SR c or a nitro group. R 1 -R 4 can be broadly substituted. R 5 is preferably a C 1-10 alkyl group, an alkenyl group, an alkynyl group, or a benzyl group. R 13 is preferably H, F or —CH 3 . R 16 is R 16 is —C(O)R f or H. The E-ring (the lactone ring) may be opened.

  通过级联自由基4+1环化合成具有公式1的化合物的方法包括步骤，其中前体2与具有公式3的芳基异腈反应，其中X是类似Cl、Br或I的基团前体。R6优选为—Si(R8R9R10)或—(R7)Si(R8R9R10)，其中R7是烷基、烯基或炔基；R8、R9和R10独立地是C1-10烷基、C2-10烯基、C2-10炔基、芳基或—(CH2)NR11基团，其中N在1到10范围内，R11是羟基、烷氧基、氨基、烷基氨基、二烷基氨基、卤素原子、氰基、—SRc或硝基。R1-R4可以广泛取代。R5优选为C1-10烷基、烯基、炔基或苄基。R13优选为H、F或—CH3。R16为C(O)R对于H。E环（内酯环）可以打开。