756488-62-7Relevant articles and documents
N -Alkylation of organonitrogen compounds catalyzed by methylene-linked bis-NHC half-sandwich ruthenium complexes
Botubol-Ares, José Manuel,Collado, Isidro G.,Jiménez-Tenorio, Manuel,Moutaoukil, Zakaria,Serrano-Díez, Emmanuel
supporting information, p. 831 - 839 (2022/02/03)
An efficient ruthenium-catalyzed N-alkylation of amines, amides and sulfonamides has been developed employing novel pentamethylcyclopentadienylruthenium(ii) complexes bearing the methylene linked bis(NHC) ligand bis(3-methylimidazol-2-ylidene)methane. The
UV-Light-Induced N-Acylation of Amines with α-Diketones
Xu, Zhihui,Yang, Tianbao,Tang, Niu,Ou, Yifeng,Yin, Shuang-Feng,Kambe, Nobuaki,Qiu, Renhua
supporting information, p. 5329 - 5333 (2021/07/21)
Herein, we develop a mild method for N-acylation of primary and secondary amines with α-diketones induced by ultraviolet (UV) light. Forty-six examples with various functional groups are explored at room temperature with irradiation by three 26 W UV lamps (350-380 nm). The yield reaches 97%. The gram scale experiment product yield is 76%. Moreover, this system can be applied to the synthesis of several amino acid derivatives. Mechanistic studies show that benzoin is generated in situ from benzil under UV irradiation.
Manganese Catalyzed Direct Amidation of Esters with Amines
Fu, Zhengqiang,Wang, Xinghua,Tao, Sheng,Bu, Qingqing,Wei, Donghui,Liu, Ning
, p. 2339 - 2358 (2021/02/03)
The transition metal catalyzed amide bond forming reaction of esters with amines has been developed as an advanced approach for overcoming the shortcomings of traditional methods. The broad scope of substrates in transition metal catalyzed amidations remains a challenge. Here, a manganese(I)-catalyzed method for the direct synthesis of amides from a various number of esters and amines is reported with unprecedented substrate scope using a low catalyst loading. A wide range of aromatic, aliphatic, and heterocyclic esters, even in fatty acid esters, reacted with a diverse range of primary aryl amines, primary alkyl amines, and secondary alkyl amines to form amides. It is noteworthy that this approach provides the first example of the transition metal catalyzed amide bond forming reaction from fatty acid esters and amines. The acid-base mechanism for the manganese(I)-catalyzed direct amidation of esters with amines was elucidated by DFT calculations.
Development of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge
Santandrea, Ernesto,Waldraff, Christine,Gerber, Gilles,Moreau, Ma?l,Beney, Pascal
supporting information, p. 1190 - 1205 (2021/05/06)
The development of the late-phase manufacturing process of the drug candidate ZPL389 and the strategies for the control of impurities are outlined in detail. Selective salt formation at several stages was pivotal to controlling the process impurities. The extensive optimization of the N-methylation of a Boc-protected amine with dimethyl sulfate and of a nucleophilic aromatic substitution without the use of metal catalysts led to a robust, scalable process. The process was demonstrated on a >100 kg scale. Overall, improved drug substance quality, higher yield, and reduction of the process mass intensity were achieved.
Direct Amidation of Carboxylic Acids through an Active α-Acyl Enol Ester Intermediate
Xu, Xianjun,Feng, Huangdi,Huang, Liliang,Liu, Xiaohui
, p. 7962 - 7969 (2018/06/18)
The development of a highly efficient and simple protocol for the direct amidation of carboxylic acids is described employing ynoates as novel coupling reagents. The transformation proceeds in good to excellent yields via in situ α-acyl enol ester intermediates formation under mild reaction conditions. This useful method has been demonstrated for a range of substrates to provide a succinct access to structurally diverse amides, including key intermediates of glibenclamide, tiapride hydrochloride, and nateglinide, and can be conducted on a mole scale.
New Initiation Modes for Directed Carbonylative C-C Bond Activation: Rhodium-Catalyzed (3 + 1 + 2) Cycloadditions of Aminomethylcyclopropanes
Wang, Gang-Wei,McCreanor, Niall G.,Shaw, Megan H.,Whittingham, William G.,Bower, John F.
supporting information, p. 13501 - 13504 (2016/10/31)
Under carbonylative conditions, neutral Rh(I)-systems modified with weak donor ligands (AsPh3 or 1,4-oxathiane) undergo N-Cbz, N-benzoyl, or N-Ts directed insertion into the proximal C-C bond of aminomethylcyclopropanes to generate rhodacyclope
Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii
Endeshaw, Molla M.,Li, Catherine,Leon, Jessica De,Yao, Ni,Latibeaudiere, Kirk,Premalatha, Kokku,Morrissette, Naomi,Werbovetz, Karl A.
scheme or table, p. 5179 - 5183 (2010/10/03)
The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasma gondii is reported. Using in vitro cultures of parasites in human fibroblasts, we determined that most of these compounds selectively disrupted Toxoplasma microtubules, and several displayed sub-micromolar potency against the parasite. The most potent compound was N1,N1-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3- benzenediamine (18b), which displayed an IC50 value of 36 nM against intracellular T. gondii. Based on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li, C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. Agents Chemother. 2010, 54, 1453], an antimitotic structure-activity relationship for dinitroanilines versus Toxoplasma is presented.
Oxidation of tertiary benzamides by 5,10,15,20-tetraphenyl- porphyrinatoironIII chloride-tert-butylhydroperoxide
Constantino, Luis,Iley, Jim
, p. 1894 - 1900 (2007/10/03)
Tertiary benzamides are oxidized by the 5,10,15,20- tetraphenylporphyrinatoiron(III) chloride-ButOOH system at the α-position of the N-alkyl groups. The major products are N-acylamides, although small amounts of secondary amides, the products of dealkylation, are also formed. Plots of initial rate versus initial substrate concentration for these reactions are curved, suggesting formation of an oxidant-substrate complex. The reaction rates are almost insensitive to the substituent in the benzamide moiety, but there is a kinetic deuterium isotope effect of 5.6 for the reaction of the N,N-(CH3)2 and N,N-(CD3) 2 compounds. Comparison of the reaction products from N-alkyl-N-methylbenzamides reveals that, for all compounds studied except N-cyclopropyl-N-methylbenzamide, oxidation of the alkyl group is preferred, strongly so (by a factor of ca. 8) for N-allyl-N-methylbenzamide. In contrast to microsomal oxidation, there is no steric hindrance to oxidation of an isopropyl group. Thus, we propose that these reactions proceed via hydrogen atom abstraction to form an α-carbon-centred radical and we attribute the observed diminished reactivity of the N-cyclopropyl group to its known reluctance to form a cyclopropyl radical. Oxidation of N-methyl-N-(2,2,3,3- tetramethylcyclopropyl)methylbenzamide provides preliminary evidence for rearrangement of an intermediate radical. While it remains unclear how these reactions proceed directly to the N-acyl products, we have established that N-hydroxymethyl, N-alkoxymethyl and N-alkylperoxymethyl intermediates are not involved.
