- Iodoarene-Catalyzed Oxyamination of Unactivated Alkenes to Synthesize 5-Imino-2-Tetrahydrofuranyl Methanamine Derivatives
-
Reported here is the room-temperature metal-free iodoarene-catalyzed oxyamination of unactivated alkenes. In this process, the alkenes are difunctionalized by the oxygen atom of the amide group and the nitrogen in an exogenous HNTs2 molecule. This mild and open-air reaction provided an efficient synthesis to N-bistosyl-substituted 5-imino-2-tetrahydrofuranyl methanamine derivatives, which are important motifs in drug development and biological studies. Mechanistic study based on experiments and density functional theory calculations showed that this transformation proceeds via activation of the substrate alkene by an in situ generated cationic iodonium(III) intermediate, which is subsequently attacked by an oxygen atom (instead of nitrogen) of amides to form a five-membered ring intermediate. Finally, this intermediate undergoes an SN2 reaction by NTs2 as the nucleophile to give the oxygen and nitrogen difunctionalized 5-imino-2-tetrahydrofuranyl methanamine product. An asymmetric variant of the present alkene oxyamination using chiral iodoarenes as catalysts also gave promising results for some of the substrates.
- Deng, Xiao-Jun,Liu, Hui-Xia,Zhang, Lu-Wen,Zhang, Guan-Yu,Yu, Zhi-Xiang,He, Wei
-
p. 235 - 253
(2021/01/09)
-
- Preparation method of 4-oxo-8-azaspiro [4.5] dec-2-ene-8-carboxylic acid tert-butyl ester (benzyl ester)
-
The invention discloses a preparation method of 4-oxo-8-azaspiro [4.5] dec-2-ene-8-carboxylic acid tert-butyl ester (benzyl ester) and an intermediate thereof. The preparation method comprises the following steps: reacting a compound II with 3-bromopropylene under the action of alkali 1 to generate a compound III; dissolving the compound III in a solvent, carrying out cyclization under the action of lithium diisopropylamide, and reacting to generate a compound IV; and under the action of alkali 2, carrying out double bond shift on the compound IV to generate a compound I. The method has the advantages of easily available raw materials, simple operation and high yield, the total yield can reach more than 65%, and the method is suitable for large-scale preparation.
- -
-
Paragraph 0055-0058
(2021/07/08)
-
- RAS INHIBITORS
-
The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.
- -
-
Paragraph 1600-1601
(2021/05/07)
-
- Novel trinitrogen-containing triheterocycles via the intramolecular nitrile oxide cycloaddition reaction
-
The intramolecular nitrile oxide cycloaddition (INOC) reaction is applied to the synthesis of novel isoxazolooxazepinoindazole, benzoisoxazolodiazepinoindazolone, and spiro[isoxazoloazepine]piperidine heterocycles. Each of these targets incorporates a uni
- Ferreira, Andrew J.,Solano, Danielle M.,Oakdale, James S.,Kurth, Mark J.
-
experimental part
p. 3241 - 3246
(2011/11/30)
-
- CGRP RECEPTOR ANTAGONISTS
-
The present invention is directed to compounds of Formula I: Formula I: I and Formula II: (where variables R1, R2, R3, R4, A, B, J, Q, T, V, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
- -
-
Page/Page column 55-56
(2010/11/08)
-
- Synthesis and structure-activity relationship of a novel sulfone series of TNF-α converting enzyme inhibitors
-
Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1- methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl} -5-piperidinecarboxamide) with a sulfonyl group led to a new series of α,β-cyclic and β,β-cyclic γ-sulfonyl hydroxamic acids, which were potent TNF-α converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy-(4S,5S)-1-methyl-5-{[4-(2-methyl-4- quinolinylmethoxy)phenyl]sulfonylmethyl}-4-pyrrolidinecarboxamide) exhibited IC50 values of 1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP-1, -2, -9 and -13 and was orally bioavailable with an F value of 46% in mice.
- Xue, Chu-Biao,Chen, Xiao-Tao,He, Xiaohua,Roderick, John,Corbett, Ronald L.,Ghavimi, Bahman,Liu, Rui-Qin,Covington, Maryanne B.,Qian, Mingxin,Ribadeneira, Maria D.,Vaddi, Krishna,Trzaskos, James,Newton, Robert C.,Duan, James J.-W.,Decicco, Carl P.
-
p. 4453 - 4459
(2007/10/03)
-
- Facile synthesis of 4-substituted-4-aminopiperidine derivatives, the key building block of piperazine-based CCR5 antagonists
-
4-Substituted-4-aminopiperidine is an interesting structural motif found in a number of bioactive compounds. An efficient and convenient method for the synthesis of 4-differently substituted-4-aminopiperidine derivatives was described, employing isonipecotate as a starting material and Curtius rearrangement as a key step. The alkylation of isonipecotate could introduce various substituents at the 4-position of the piperidine ring. With this key building block, we are able to efficiently synthesize piperazino-piperidine based CCR5 antagonist in a highly convergent manner free of using toxic reagents such as diethylaluminum cyanide. The concise synthesis of a potent bioavailable CCR5 antagonist as HIV-1 entry inhibitor, Sch-350634 (1) was accomplished in excellent yield using N′-Boc-4-methyl-4-aminopiperidine 5a as a smart building block. The new methodology provides a facile and practical access to the piperazino-piperidine amide analogs as HIV-1 entry inhibitors.
- Jiang, Xiao-Hua,Song, Yan-Li,Long, Ya-Qiu
-
p. 3675 - 3678
(2007/10/03)
-
