(3-(tert-butoxycarbonylamino)naphthalen-1-yl)carbamic acid tert-butyl ester | 483349-24-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (3-(tert-butoxycarbonylamino)naphthalen-1-yl)carbamic acid tert-butyl ester
• 英文别名: N,N′-bis(tert-butoxycarbonyl)naphthalene-1,3-diamine；N,N'-bis(tert-butyloxycarbonyl)-1,3-naphthalenediamine；naphthalene-1,3-(bis-tertbutoxycarbamate)；tert-butyl N-[3-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]carbamate
• CAS: 483349-24-2
• 化学式: C₂₀H₂₆N₂O₄
• 分子量: 358.437
• InChiKey: VKHVSXSEZRKICP-UHFFFAOYSA-N

物化性质

• 熔点：
  129-131 °C(Solv: ligroine (8032-32-4))
• 沸点：
  424.0±28.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3-(tert-butoxycarbonylamino)naphthalen-1-yl)carbamic acid tert-butyl ester 在 Grubbs catalyst first generation 四氯化碳 、 N-碘代丁二酰亚胺 、 三正丁基氢锡 、 sodium hydride 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 30.25h， 生成 (2E)-1-[5-amino-1-(chloromethyl)-1H,2H,3H-benzo[e]indol-3-yl]-3-(4-methoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  3-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚（氨基-CBI）的新短合成。

  摘要：

  公开了一种来自Martius Yellow的3-取代的5-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚的新的短合成物。合成的关键步骤是三个有效的区域选择性反应（碘化，5-exo-trig芳基自由基-烯烃环化和羧化）。

  DOI：

  10.1021/jo0263115
• 作为产物：
  描述：

  1,3-二硝基萘 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 60.0 ℃ 、101.33 kPa 条件下， 反应 16.0h， 生成 (3-(tert-butoxycarbonylamino)naphthalen-1-yl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
  [FR] DIMÈRES D'ISOQUINOLIDINOBENZODIAZÉPINE (IQB)-1(CHLOROMÉTHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI)

  摘要：

  本文提供了异喹啉苯二氮卓啶（IQB）-1（氯甲基）-2,3-二氢-1H-苯并[e]吲哚（CBI）二聚体，包括它们的抗体药物结合物，以及用于杀灭细胞和治疗疾病的方法。

  公开号：

  WO2018071455A1

文献信息

• Observation by NMR of cationic Wheland-like intermediates in the deiodination of protected 1-iodonaphthalene-2,4-diamines in acidic media
  作者：Elvis A. Twum、Timothy J. Woodman、Wenyi Wang、Michael D. Threadgill

  DOI：10.1039/c3ob41386a

  日期：——

  1-Iodonaphthalene-2,4-diamines in trifluoroacetic acid/chloroform give stable Wheland-like tetrahedral cationic species observable by NMR, through an initial intramolecular protonation. Dynamic equilibria allow proton-deuterium exchange of aromatic protons and provide a mechanism for deiodination of 1-iodonaphthalene-2,4-diamines.

  在三氟乙酸/氯仿中，1-碘萘-2,4-二胺通过最初的分子内质子化作用，产生了可通过核磁共振观测到的稳定的惠兰四面体阳离子物种。动态平衡允许芳香质子进行质子-氘交换，为 1-碘萘-2,4-二胺的脱碘反应提供了一种机制。
• [EN] PROCESSES FOR PREPARING 3-SUBSTITUTED 1-(CHLOROMETHYL)-1,2-DIHYDRO-3H-[RING FUSED INDOL-5-YL(AMINE-DERIVED)] COMPOUNDS AND ANALOGUES THEREOF, AND TO PRODUCTS OBTAINED THEREFROM<br/>[FR] PROCEDE DE PREPARATION DE COMPOSES DE 3-SUBSTITUE 1-(CHLOROMETHYL)-1,2-DIHYDRO-3H [-5-YL A CYCLES FUSIONNES (DERIVES D'AMINE)] ET DE LEURS ANALOGUES, ET PRODUITS DERIVES
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2003097635A1

  公开（公告）日：2003-11-27

  The invention provides processes of preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3H-[ring fused indol-5-yl(amine-derived)] compounds of formula (I) and its analogues, or a physiologically functional derivative thereof, (I), wherein A and B together may represent a fused optionally substituted benzene, naphthalene, pyridine, furan or a pyrrole ring, where the optional substituents are represented by Y; X is halogen or OSO2R , and W is selected from NO2, NHOH, N(R3)2NHR3, NHCO2R3, N(phthaloyl) or NH2, or W is further selected from the group (a) , wherein J is selected from OH or R, and P is a group which is a substrate suitable for a nitroreductase or carboxypeptidase enzyme. The invention is also directed to the use of compounds of formula (I) prepared by the processes of the invention as cytotoxins for cancer therapy and as prodrugs for gene-directed enzyme-prodrug therapy (GDEPT) and antibody-directed enzyme-prodrug therapy (ADEPT).

  该发明提供了制备公式（I）及其类似物的3-取代1-(氯甲基)-1,2-二氢-3H-[环融合吲哚-5-基（衍生自胺基）]化合物的过程，或其生理功能衍生物，其中A和B一起可以表示一个融合的可选取代苯、萘、吡啶、呋喃或吡咯环，其中可选取代基由Y表示；X为卤素或OSO2R，W从NO2、NHOH、N(R3)2NHR3、NHCO2R3、N(邻苯二甲酰基)或NH2中选择，或W进一步从群（a）中选择，其中J从OH或R中选择，P是适用于硝基还原酶或羧肽酶的底物基团。该发明还涉及通过该发明的过程制备的公式（I）化合物作为抗癌细胞毒素以及基因导向酶-前药疗法（GDEPT）和抗体导向酶-前药疗法（ADEPT）的前药的用途。
• Isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers
  申请人：Cellerant Therapeutics, Inc.

  公开号：US10350218B2

  公开（公告）日：2019-07-16

  Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.

  本文提供了异喹啉并二氮杂卓（IQB）-1（氯甲基）-2,3-二氢-1H-苯并[e]吲哚（CBI）二聚体、包含它们的抗体-药物共轭物以及用于杀死细胞和治疗疾病的方法。
• Initial development of a cytotoxic amino-seco-CBI warhead for delivery by prodrug systems
  作者：Elvis A. Twum、Amit Nathubhai、Pauline J. Wood、Matthew D. Lloyd、Andrew S. Thompson、Michael D. Threadgill

  DOI：10.1016/j.bmc.2015.04.034

  日期：2015.7

  Cyclopropabenzaindoles (CBIs) are exquisitely potent cytotoxins which bind and alkylate in the minor groove of DNA. They are not selective for cancer cells, so prodrugs are required. CBIs can be formed at physiological pH by Winstein cyclisation of 1-chloromethyl-3-substituted-5-hydroxy-2,3-dihydro-benzo[e] indoles (5-OH-seco-CBIs). Corresponding 5-NH2-seco-CBIs should also undergo Winstein cyclisation similarly. A key triply orthogonally protected intermediate on the route to 5-NH2-seco-CBIs has been synthesised, via selective monotrifluoroacetylation of naphthalene-1,3-diamine, Boc protection, electrophilic iodination, selective allylation at the trifluoroacetamide and 5-exo radical ring-closure with TEMPO. This intermediate has potential for introduction of peptide prodrug masking units (deactivating the Winstein cyclisation and cytotoxicity), addition of diverse indole-amide side-chains (enhancing non-covalent binding prior to alkylation) and use of different leaving groups (replacing the usual chlorine, allowing tuning of the rate of Winstein cyclisation). This key intermediate was elaborated into a simple model 5-NH2-seco-CBI with a dimethylaminoethoxyindole side-chain. Conversion to a bio-reactive entity and the bioactivity of this system were confirmed through DNA-melting studies (Delta T-m = 13 degrees C) and cytotoxicity against LNCaP human prostate cancer cells (IC50 = 18 nM). (C) 2015 Elsevier Ltd. All rights reserved.
• ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
  申请人：Cellerant Therapeutics, Inc.

  公开号：US20180177795A1

  公开（公告）日：2018-06-28

  Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.