- alpha-monodeuterated amine compound, deuterated medicine and preparation method of same
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The invention relates to an alpha-monodeuterated amine compound and a reduction deuteration method of an oxime compound for preparing the alpha-monodeuterated amine compound. The method is characterized in that an oxime compound as shown in a general formula (1) reacts with a divalent lanthanide transition metal compound and a deuterium donor reagent in an organic solvent I to generate the alpha-monodeuterated amine compound as shown in a general formula (2), optionally, the compound shown in the general formula (2) is added into an organic acid and/or inorganic acid-organic solvent solution to obtain the ammonium salt shown in the general formula (2). The invention overcomes the defects that the preparation method of the alpha-monodeuterated amine compound in the prior art needs to adopt an expensive and highly toxic transition metal catalyst or an expensive and flammable metal deuteride and generates toxic by-products.
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Paragraph 0139-0142
(2021/05/29)
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- Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D2O as a Deuterium Source
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Selective introduction of the deuterium atom into the α-position of amines is important for the development of all types of novel deuterated drugs and agrochemicals due to the pervasive presence of amines. In this study, we report the first general single-electron-transfer reductive deuteration of both ketoximes and aldoximes using SmI2 as an electron donor and D2O as a deuterium source for the synthesis of α-deuterated primary amines with excellent levels of deuterium incorporations (>95% [D]). This protocol exhibits excellent chemoselectivity and tolerates a variety of functional groups. The potential application of this new method was showcased in the synthesis of deuterated drugs, such as rimantadine-d4, the tebufenpyrad analogue, derivatives of nabumetone and pregnenolone, and a series of building blocks for the rapid and general assembly of deuterated drugs and pesticides.
- Ning, Lei,Li, Hengzhao,Lai, Zemin,Szostak, Michal,Chen, Xingyue,Dong, Yanhong,Jin, Shuhui,An, Jie
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p. 2907 - 2916
(2021/02/27)
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- Stable isotope deuterium-labeled rimantadine hydrochloride and synthesis method thereof
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The invention discloses stable isotope deuterium-labeled rimantadine hydrochloride and a synthesis method thereof. The synthesis method comprises the following steps: S1, reacting adamantane formyl chloride with deuterated methyl iodide to prepare deuterated adamantane methyl ketone; S2, enabling deuterated adamantane methyl ketone to react with hydroxylamine hydrochloride to prepare deuterated adamantane methyl ketoxime; and S3, reducing the deuterated adamantane methyl ketoxime by lithium aluminum deuteride, and adding hydrochloric acid for salifying to obtain the stable isotope deuterium-labeled rimantadine hydrochloride. The synthesis process is short in route, simple in process and mild in condition, the stable isotope deuterium cannot fall off, a product labeled by the stable isotopedeuterium at a specific position can be obtained, the product is easy to separate and purify and high in yield, the chemical purity and the stable isotope abundance of the obtained product both reach99% or above, and the requirements of serving as a standard reagent for quantitatively detecting the rimantadine hydrochloride are met; and the use value is high, and good economy is achieved.
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Paragraph 0023; 0027-0029; 0030; 0034
(2021/01/29)
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