762240-92-6Relevant articles and documents
Green synthesis method of sitagliptin intermediate
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Paragraph 0032; 0044-0047; 0051-0052; 0056-0059, (2021/10/27)
The invention relates to a green synthesis method of sitagliptin intermediate, and belongs to the technical field of drug intermediate synthesis. In order to solve the problems that an existing pollution is large and unstable, a green synthesis method of sitagliptin intermediate is provided, and the method comprises the following steps: in an ether solvent, reacting trifluoroacetic acid ethyl ester with ethylenediamine to generate 2 - trifluoroacetamide ethyl ethylamine. Under the presence of an acid binding agent, 2 - trifluoroacetamide ethyl ethylamine and halogenated ethyl acetate are condensed and reacted under the conditions of 45 °C - 65 °C DEG C to form an intermediate, and then, the temperature is raised to 90 - 110 °C for cyclization reaction to generate N - trifluoroacetyl piperidine. The N -trifluoroacetyl piperidine ketone is reacted with hydrazine hydrate to generate 1 -trifluoroacetylamino -2 -piperazinone. The product is reacted with hydrochloric acid to form a ring-forming reaction, and a product sitagliptin intermediate is obtained. The method provided by the invention has the advantages of high product yield and purity on the whole, and has the advantage of environmental friendliness.
Preparation method of sitagliptin intermediate
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Paragraph 0024; 0030; 0034-0035; 0039-0040; 0044-0045; 0049, (2021/02/13)
The invention relates to a preparation method of a sitagliptin intermediate, and belongs to the technical field of drug intermediate synthesis. In order to solve the problems of low product yield andpoor environmental protection property in the prior art, the invention provides a preparation method of a sitagliptin intermediate, and the method comprises the following steps: reacting 2-piperazinone with hydrazine hydrate in an alcohol solvent to generate piperazine hydrazone; in an acetonitrile or ether solvent, reacting the piperazine hydrazone with ethyl trifluoroacetate to obtain a corresponding intermediate N -[(2Z-) piperazine -2-subunit] trifluoroacethydrazide; and performing cyclization and salification reaction on the N -[(2Z-) piperazine -2-subunit] trifluoroacethydrazide in an alcohol solvent under the action of hydrochloric acid to obtain the corresponding sitagliptin intermediate 3-trifluoromethyl 5, 6, 7, 8-tetrahydro-1, 2, 4-triazole [4, 3-a] pyrazine hydrochloride. The reaction has the effects of high selectivity and high product yield.
Urea and thiourea derivatives of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine: Synthesis, characterization, antimicrobial activity and docking studies
Mannam, Madhava Rao,Devineni, Subba Rao,Pavuluri, Chandra Mouli,Chamarthi, Naga Raju,Kottapalli, Raja Sekhara P.
, p. 922 - 932 (2019/03/07)
An efficient and robust synthetic procedure was developed primarily for the synthesis of a precursor compound; 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine (11), from 2-chloropyrazine (7) through the chemical transformations such as hydrazine substitution, trifluoroacetyl group induction, cyclization and pyrazine ring reduction. A new series of urea derivatives 13a-e and thiourea derivatives 13f-j of compound 11 have been synthesized and the structures of all the compounds were confirmed using spectroscopic analyses such as IR, 1H NMR, 13C NMR, LC-MS and HRMS. The newly synthesized compounds were screened for their in vitro antimicrobial activity against five bacteria and two fungi, in which compounds 13d, 13i and 13j displayed potential activity against bacterial strains and 13a, 13d, 13g and 13j against fungal strains with the MIC values in the range of 6.25–25.0 μg/mL. An overall comparison of the activity results revealed that thiourea derivatives contain better activity than that of urea compounds. Molecular docking studies on poly (ADP-ribose) polymerase 15 (ARTD7, BAL3) demonstrated that all the synthesized compounds possess significant binding energies (-8.1 to -9.8 kcal/mol) with no adverse effect in the active site of protein.