367-22-6Relevant articles and documents
Catalyst-Controlled Regioselective Chlorination of Phenols and Anilines through a Lewis Basic Selenoether Catalyst
Dinh, Andrew N.,Maddox, Sean M.,Vaidya, Sagar D.,Saputra, Mirza A.,Nalbandian, Christopher J.,Gustafson, Jeffrey L.
, p. 13895 - 13905 (2020/11/03)
We report a highly efficient ortho-selective electrophilic chlorination of phenols utilizing a Lewis basic selenoether catalyst. The selenoether catalyst resulted in comparable selectivities to our previously reported bis-thiourea ortho-selective catalyst, with a catalyst loading as low as 1%. The new catalytic system also allowed us to extend this chemistry to obtain excellent ortho-selectivities for unprotected anilines. The selectivities of this reaction are up to >20:1 ortho/para, while the innate selectivities for phenols and anilines are approximately 1:4 ortho/para. A series of preliminary studies revealed that the substrates require a hydrogen-bonding moiety for selectivity.
CD4 mimics as HIV entry inhibitors: Lead optimization studies of the aromatic substituents
Narumi, Tetsuo,Arai, Hiroshi,Yoshimura, Kazuhisa,Harada, Shigeyoshi,Hirota, Yuki,Ohashi, Nami,Hashimoto, Chie,Nomura, Wataru,Matsushita, Shuzo,Tamamura, Hirokazu
, p. 2518 - 2526 (2013/06/26)
Several CD4 mimics have been reported as HIV-1 entry inhibitors that can intervene in the interaction between a viral envelope glycoprotein gp120 and a cell surface protein CD4. Our previous SAR studies led to a finding of a highly potent analogue 3 with bulky hydrophobic groups on a piperidine moiety. In the present study, the aromatic ring of 3 was modified systematically in an attempt to improve its antiviral activity and CD4 mimicry which induces the conformational changes in gp120 that can render the envelope more sensitive to neutralizing antibodies. Biological assays of the synthetic compounds revealed that the introduction of a fluorine group as a meta-substituent of the aromatic ring caused an increase of anti-HIV activity and an enhancement of a CD4 mimicry, and led to a novel compound 13a that showed twice as potent anti-HIV activity compared to 3 and a substantial increase in a CD4 mimicry even at lower concentrations.
Robust synthesis of methyl 5-chloro-4-fluoro-1 h -indole-2-carboxylate: A key intermediate in the preparation of an HIV NNRTI candidate
Mayes, Benjamin A.,Chaudhuri, Narayan C.,Hencken, Christopher P.,Jeannot, Frederic,Latham, G. Mark,Mathieu, Steven,Mcgarry, F. Patrick,Stewart, Alistair J.,Wang, Jingyang,Moussa, Adel
body text, p. 1248 - 1253 (2011/04/18)
A synthetic preparation of methyl 5-chloro-4-fluoro-1H-indole-2- carboxylate, a key intermediate towards phosphoindole inhibitors of HIV non-nucleoside reverse transcriptase, is described. The five-step synthesis involved Boc protection of the commercially available 4-chloro-3-fluoroaniline and regioselective iodination at C-2. After facile Boc deprotection, cyclization of the resultant o-iodoaniline gave the corresponding 5-chloro-4-fluoro-indole- 2-carboxylic acid which was subsequently esterified to provide the target indole ester in 56% overall yield. Identification of 6-chloro-7-iodo-2(3H)- benzoxazolone as a significant side product in the iodination step led to the development of conditions which eliminated its formation in subsequent batches. Advantages of this alternative approach relative to existing methodologies include (1) potentially hazardous diazonium and azido species were not required, (2) regioisomeric products were not generated, and (3) chromatographic isolations were avoided, as all intermediates were easily crystallized. As a result, the key indole ester was produced rapidly at 100-fold increased scale compared to previous reports with a 10-fold improvement in overall yield.
