4169-19-1Relevant academic research and scientific papers
Method for promoting acylation of amine or alcohol by carbon dioxide
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Paragraph 0033-0034, (2021/05/29)
The invention relates to a method for promoting acylation of amine or alcohol by carbon dioxide, which comprises the following steps of: mixing an amine compound, carboxylate or thiocarboxylate compound and a reaction solvent under the action of carbon dioxide, and reacting to obtain an amide compound, or under the action of carbon dioxide, mixing the alcohol compound, the thiocarboxylate compound and the reaction solvent [gamma]-valerolactone, and reacting to obtain the ester compound. According to the invention, under the promotion action of carbon dioxide, carboxylate or thiocarboxylate is used as an acylation reagent, and amine and alcohol are converted into amide and ester compounds in the absence of a transition metal catalyst, so that acylation reagents such as acyl chloride or anhydride with irritation and corrosivity are avoided; and the method has the advantages of simple operation, mild reaction conditions, high tolerance of substrate functional groups, strong applicability and high yield, and provides an efficient, reliable and economical preparation method for synthesis of amide and ester compounds.
Environmentally benign decarboxylative: N-, O-, and S-Acetylations and acylations
Ghosh, Santanu,Purkait, Anisha,Jana, Chandan K.
supporting information, p. 8721 - 8727 (2020/12/30)
An operationally simple and general method for acetylation and acylation of a wide variety of substrates (amines, alcohols, phenols, thiols, and hydrazones) has been reported. Meldrum's acid and its derivatives have been used as an air-stable, non-volatile, cost-effective, and easy to handle acetylating/acylating agent. Easily separable byproducts (CO2 and acetone) allowed the isolation of analytically pure acetylated products without the requirement of work-up and any chromatography. This journal is
Multi-Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
Li, Yushu,Wong, Luet L.
supporting information, p. 9551 - 9555 (2019/08/06)
Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L?1 day?1). Other oxidase activities, such as C?C bond desaturation, aromatization, and C?C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.
Radical C(sp3)-H alkenylation, alkynylation and allylation of ethers and amides enabled by photocatalysis
Paul, Subhasis,Guin, Joyram
supporting information, p. 2530 - 2534 (2017/07/17)
An efficient radical addition/elimination reaction that enables selective incorporation of alkenyl, alkynyl and allyl functional groups into the C(sp3)-H bond under green reaction conditions is developed. The process is based on the catalytic formation of α-alkoxyl/α-amidyl radicals via the homolytic activation of the C(sp3)-H bond of ethers/amides with a catalytic amount of diarylketone in the presence of a household fluorescent light bulb. This simple reaction protocol features good functional group tolerance, scalability, convenient reagents and operating systems. Synthetic application of the method has been demonstrated via the preparation of natural products and different valuable synthones.
A Unique Approach to Design Potent and Selective Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP) Inhibitors
Bronner, Sarah M.,Murray, Jeremy,Romero, F. Anthony,Lai, Kwong Wah,Tsui, Vickie,Cyr, Patrick,Beresini, Maureen H.,De Leon Boenig, Gladys,Chen, Zhongguo,Choo, Edna F.,Clark, Kevin R.,Crawford, Terry D.,Jayaram, Hariharan,Kaufman, Susan,Li, Ruina,Li, Yingjie,Liao, Jiangpeng,Liang, Xiaorong,Liu, Wenfeng,Ly, Justin,Maher, Jonathan,Wai, John,Wang, Fei,Zheng, Aijun,Zhu, Xiaoyu,Magnuson, Steven
, p. 10151 - 10171 (2018/01/10)
The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region and then building into the LPF shelf. Herein, we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family.
THERAPEUTIC COMPOUNDS AND USES THEREOF
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Page/Page column 144, (2017/12/29)
The present invention relates to compounds of formula (I) and formula (II): and to salts thereof, wherein R1-R4 of formula (I) and R5-R6 of formula (II) have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II), or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.
Interception of amide ylides with sulfonamides: Synthesis of (: E)- N -sulfonyl amidines catalyzed by Zn(OTf)2
Chen, Jijun,Long, Wenhao,Fang, Shangwen,Yang, Yonggang,Wan, Xiaobing
supporting information, p. 13256 - 13259 (2017/12/26)
Through the interception of amide ylides with sulfonamides, we herein report the first general example of an intermolecular condensation reaction between sulfonamides and amides. Beyond formamides, this approach was successfully applied to a variety of lactams and linear amides, giving rise to a broad array of (E)-N-sulfonyl amidines.
Synthesis of 6-nitro-1,2,3,4-tetrahydroquinoline: An experimental and theoretical study of regioselective nitration
Cordeiro, Alessandra,Shaw, Julian,O'Brien, John,Blanco, Fernando,Rozas, Isabel
experimental part, p. 1504 - 1513 (2011/04/25)
A revision of the literature on the nitration of tetrahydroquinolines yielded a number of inconsistencies. Thus, we have carried out a thorough study on the nitration of tetrahydroquinoline and several of its N-protected derivatives both experimentally and at theoretical level. Usually, nitration is carried out in acidic conditions and, thus, tetrahydroquinoline would be N-protonated; however, if the amino group is protected, the neutral system will be the one undergoing nitration. Different protecting groups have been explored varying, not only electronic and steric effects, but also deprotection conditions. Additionally, different reagents and reaction conditions have been investigated. From this study we have been able to achieve total regioselectivity for nitration at the 6-position. A very detailed NMR study has been carried out to unequivocally characterise the four nitro isomers. In parallel, a computational study has been performed that is in agreement with the experimental results obtained. With this purpose, all the σ complexes of the four nitro isomers neutral and N-protonated have been optimized both in gas and water condensed phases by using the B3LYP/6-31++G* level of computation. The selective nitration of tetrahydroquinoline was studied. N-Protecting groups presence or absence directs nitration at different positions. Regioselective nitration at 6-position was achieved. A DFT computational study of all nitro σ complexes was performed in gas and water phases, the results are consistent with the experiments. Copyright
Substituted Spiroamide Compounds
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Page/Page column 22, (2010/09/18)
Substituted spiroamide compounds corresponding to formula (I): wherein A, B, Q1, Q2, Q3, Q4, R1, R8, R9a, R9b, R12, R13, R200 and R210 have defined meanings, processes for their preparation, pharmaceutical compositions containing such compounds, and the use of such compounds for treating or inhibiting pain or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).
A facile one-pot synthesis of N-substituted tetrahydroquinolines
Babu, Thelagathoti Hari,Shanthi, Gnanamani,Perumal, Paramasivan T.
experimental part, p. 2881 - 2884 (2009/09/06)
An uncatalyzed one-pot synthesis of N-substituted tetrahydroquinolines was achieved in good yields by the reaction of quinoline and alkyl/acyl halides with Hantzsch dihydropyridine ester under mild reaction conditions.
