N-(triphenylmethyl)-4-chloro-2-(trifluoroacetyl)aniline | 209460-09-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-(triphenylmethyl)-4-chloro-2-(trifluoroacetyl)aniline
• 英文别名: 1-[5-chloro-2-(tritylamino)phenyl]-2,2,2-trifluoroethan-1-one；N-Triphenylmethyl-4-chloro-2-trifluoroacetylaniline；1-[5-chloro-2-(tritylamino)phenyl]-2,2,2-trifluoroethanone
• CAS: 209460-09-3
• 化学式: C₂₇H₁₉ClF₃NO
• 分子量: 465.902
• InChiKey: LEFWQCCBPBNBBO-UHFFFAOYSA-N

物化性质

• 熔点：
  165-167 °C
• 沸点：
  546.6±50.0 °C(Predicted)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(triphenylmethyl)-4-chloro-2-(trifluoroacetyl)aniline 在 盐酸 、 正丁基锂 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.75h， 生成 2-氨基-5-氯-alpha-(2-环丙基乙炔基)-alpha-(三氟甲基)苯甲醇
  参考文献：
  名称：

  4,1-Benzoxazepinone analogues of efavirenz (Sustiva™) as HIV-1 reverse transcriptase inhibitors

  摘要：

  A series of 4,1-benzoxazepinone analogues of efavirenz (Sustiva(TM)) as potent NNRTIs has been discovered. The cis-3-alkylbenzoxazepinones are more potent then the trans isomers and can be synthesized preferentially by a novel stereoselective cyclization. The best compounds are potent orally bioavailable inhibitors of both wild-type HIV-1 and its clinically relevant K103N mutant virus, but are highly protein-bound in human plasma. (C) 2001 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00239-6
• 作为产物：
  描述：

  4'-氯代新戊酰苯胺 在 sodium acetate 、 对甲苯磺酸 作用下， 反应 6.0h， 生成 N-(triphenylmethyl)-4-chloro-2-(trifluoroacetyl)aniline
  参考文献：
  名称：

  Practical Asymmetric Synthesis of Efavirenz (DMP 266), an HIV-1 Reverse Transcriptase Inhibitor

  摘要：

  A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) top-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.

  DOI：

  10.1021/jo981170l

文献信息

• NHC-Copper(I) Halide-Catalyzed Direct Alkynylation of Trifluoromethyl Ketones on Water
  作者：Paweł Czerwiński、Edyta Molga、Luigi Cavallo、Albert Poater、Michał Michalak

  DOI：10.1002/chem.201601581

  日期：2016.6.6

  Br, I, OAc, OTf) complexes, providing tertiary propargylic trifluoromethyl alcohols in high yields and with excellent chemoselectivity from a broad range of aryl‐ and more challenging alkyl‐substituted trifluoromethyl ketones (TFMKs). DFT calculations were performed to rationalize the correlation between the yield of catalytic alkynylation and the sterics of N‐heterocyclic carbenes (NHCs), expressed

  据报道，首次在水上进行的高效，易扩展的NHC-铜（I）卤化物催化的末端炔烃加成至1,1,1-三氟甲基酮中。使用少至0.1–2.0 mol％的[（NHC）CuX]（X = Cl，Br，I，OAc，OTf）络合物进行一系列加成反应，从而以高收率和优异的化学选择性提供叔炔丙基三氟甲醇。来自各种芳基和更具挑战性的烷基取代的三氟甲基酮（TFMK）。进行DFT计算以合理化催化炔基化收率与N-杂环卡宾（NHCs）的空间之间的相关性，以掩埋体积（％VBur）表示，表明空间效应支配了反应的产率。额外的DFT计算为TFMK烷基化中[（NHC）CuX]配合物的差异反应性提供了一些启示。在C存在下的直接炔基化反应的第一个对映体选择性形式还介绍了1个对称的NHC-铜（I）配合物。
• Asymmetric synthesis of benzoxazinones
  申请人：DuPont Pharmaceuticals Company

  公开号：US05925789A1

  公开（公告）日：1999-07-20

  The present invention provides novel methods for the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1- benzoxazin-2-one of formula (VI-i) ##STR1## which is useful as a human immunodeficiency virus (HIV) reverse transcriptase inhibitor.

  本发明提供了一种新颖的方法，用于不对称合成式（VI-i）的（S）-6-氯-4-环丙基乙炔基-4-三氟甲基-1,4-二氢-2H-3,1-苯并噁唑-2-酮，该化合物对人类免疫缺陷病毒（HIV）逆转录酶具有抑制作用。
• The First Proline-Catalyzed Friedlander Annulation: Regioselective Synthesis of 2-Substituted Quinoline Derivatives
  作者：Biao Jiang、Jia-jia Dong、Yun Jin、Xiao-long Du、Min Xu

  DOI：10.1002/ejoc.200800121

  日期：2008.6

  The first proline-catalyzed Friedlander annulation for the synthesis of 2-substituted 4-trifluoromethyl quinoline derivatives is described. Excellent re gio selectivity as well as good yields were shown in a variety of cases, and a tandem aldol-cyclization pathway might be involved. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

  描述了第一个用于合成 2-取代 4-三氟甲基喹啉衍生物的脯氨酸催化 Friedlander 环化。在各种情况下都显示出优异的区域选择性和良好的产率，并且可能涉及串联醛醇环化途径。((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)。
• [EN] ASYMMETRIC SYNTHESIS OF BENZOXAZINONES VIA NEW INTERMEDIATES<br/>[FR] SYNTHESE ASYMETRIQUE DE BENZOXAZINONES VIA DE NOUVEAUX INTERMEDIAIRES
  申请人：DU PONT PHARMACEUTICALS COMPANY

  公开号：WO1998045278A1

  公开（公告）日：1998-10-15

  (EN) The present invention provides novel methods for the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one of formula (VI-i) which is useful as a human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In an embodiment, the present invention provides a process for the preparation of an amino alcohol compound of formula (V-i) comprising adding a toluene solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to a toluene solution of a compound of formula (III-i), via a compound of formula (IV-i).(FR) Nouveaux procédés pour la synthèse asymétrique de (S)-6-chloro-4-cyclopropyléthynyl-4-trifluorométhyl-1,4-dihydro-2H-3,1-benzoxazin-2-one de formule (VI-i), qui est utile comme inhibiteur de la transcriptase inverse du virus de l'immunodéficience humaine (VIH). Dans un mode de réalisation, l'invention concerne un procédé pour préparer un composé amino-alcool de formule (V-i), consistant à ajouter une solution de toluène de 2,3-dichloro-5,6-dicyano-1,4 benzoquinone à une solution de toluène d'un composé de formule (III-i) via un composé de formule (IV-i).

  本发明提供了一种新颖的方法，用于不对称合成(S)-6-氯-4-环丙基乙炔基-4-三氟甲基-1,4-二氢-2H-3,1-苯并噁唑-2-酮的化合物，化合物的化学式为(VI-i)，该化合物可用作人类免疫缺陷病毒(HIV)反转录酶抑制剂。在一种实施例中，本发明提供了一种制备化合物的氨基醇的方法，该化合物的化学式为(V-i)，包括向化合物的甲苯溶液中加入化合物的化学式为(III-i)的甲苯溶液，通过化合物的化学式为(IV-i)。
• In Situ Recycling of Chiral Ligand and Surplus Nucleophile for a Noncatalytic Reaction:  Amplification of Process Throughput in the Asymmetric Addition Step of Efavirenz (DMP 266)
  作者：Anusuya Choudhury、James R. Moore、Michael E. Pierce、Joseph M. Fortunak、Ioannis Valvis、Pat N. Confalone

  DOI：10.1021/op025595s

  日期：2003.5.1

  The synthesis of efavirenz (DMP 266) involves a highly enantioselective asymmetric reaction of ketone 2a with lithium cyclopropylacetylide 3a in the presence of (1R,2S)-pyrrolidinylnorephedrine (PNE) 4b as the chiral mediator to produce 6b, a key advance intermediate bearing a tetrasubstituted chiral carbon. The major drawback of this reaction is that it requires at least 2 mol of cyclopropylacetylene (CPA) 3b, 2 mol of the chiral mediator 4b, and 4 mol of an n-alkyllithimn base to generate a 1 mol of addition product 6b. In a program to improve the cost-effectiveness of the process, we have studied this asymmetric addition reaction to reduce the stoichiometry of the chiral moderator and CPA nucleophile. The initial experimental designs to improve the stoichiometry were based on the assumption that the second equivalent of lithium cyclopropylacetylide simply acted as a base to deprotonate the N-H of ketones 2a or 2b, leaving 1 equiv of unlithiated and presumably unreactive CPA. It was reasoned that if we lithiate this CPA in the postreaction mixture, it would complex with the already lithiated ligand in the reaction which could then be used to convert additional 2a or 2b into product thus improving the stoichiometry. After some trial experiments, a dramatic decrease in stoichiometry was achieved and it was found that by simply adding one more equivalent of an n-alkyllithium to the system after the first reaction cycle, it was possible to obtain at least a 14 % throughput increase with just a 5% dilution of the reaction volume in this simple and more cost-efficient process. The chiral addition reactions could be run with multiple cycles in the same pot with the sequential addition of n-alkyllithium 5, CPA 3b, and ketone 2a. However, after four cycles, there was some decrease in the enantioselectivities (90.8%) that ultimately places a practical limit on the number of recycles possible. The process throughput increase can be explained in the light of a recent mechanistic investigation by Collum and co-workers. We postulate that the introduction of an n-alkyllithium to the reaction mixture after the completion of the first cycle regenerates the reactive cubic