196597-27-0Relevant articles and documents
A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides
Pedersen, Simon S.,Donslund, Aske S.,Mikkelsen, Jesper H.,Bakholm, Oskar S.,Papp, Florian,Jensen, Kim B.,Gustafsson, Magnus B. F.,Skrydstrup, Troels
supporting information, p. 7114 - 7123 (2021/03/03)
A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled NiII-acyl complexes, formed from a 13CO insertion step with NiII-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII-acyl complexes and the disulfide providing a reactive NiIII-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.
Synthetic method of ramelteon
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, (2019/12/02)
The invention discloses a synthesis method of ramelteon. The method comprises the following steps: based on commercially available compounds 4-amino-2,3-dihydrobenzofuran, under the reacting functionof sulfuric acid, sodium nitrite and potassium iodide, an aryl ammonia compound is converted into an aryl iodine compound; allowing the obtained aryl iodine compound to react with a bromo allyl alcohol compound under the action of a palladium catalyst, an inorganic base, a phosphine ligand, a norbornene derivative and an additive to obtain an aldehyde group-containing ramelteon intermediate; finally, the intermediate and propionamide are subjected to a reductive amination reaction under the action of trifluoroacetic acid and triethylsilane, a target compound ramelteon is obtained, the reactioncomprises three steps in total, and the total yield is 26%. Compared with the prior art, the synthesis method disclosed by the invention has the advantages that the target molecule ramelteon can be obtained from the commercially available compound 4-amino-2, 3-dihydrobenzofuran which is easy to prepare only by three steps, the synthesis steps are greatly shortened compared with other process routes, the steps are few, and the safety is high.
A process for the preparation of key intermediate lei meiti amine, its preparation and use
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, (2020/02/07)
The invention discloses critical intermediates (with the structure formula (I) ) used for preparing ramelteon. In the formula (I), A is O or S; R is hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, tert-butyl, cyclobutyl, n-pentyl, isopentyl, cyclopentyl, phenyl, benzyl or p-methoxybenzyl; and when chiral carbon exists, the chemical compounds in the formula (I) are racemate or optically active compounds. When the A in the formula (I) is O and the R in the formula (I) is ethyl, the chemical compound is the chemical compound shown as the structure formula (II). In addition, the invention further discloses a preparing method of the chemical compound shown as the formula (II) and applications of the formula (II) in preparation of the ramelteon used for treating insomnia.
