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762240-92-6Relevant academic research and scientific papers
Preparation method of sitagliptin intermediate
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Paragraph 0074-0076, (2021/06/22)
The invention discloses a preparation method of a sitagliptin intermediate. The preparation method of the sitagliptin intermediate comprises the following step: in a solvent, carrying out a reaction as shown in the specification on a compound as shown in a formula 2 and a compound as shown in a formula 3 to obtain a compound as shown in a formula 4. The preparation method is high in yield, avoids the use of explosive reagents and phosphorus oxychloride, and is suitable for industrial production.
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.
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 0036, (2020/07/15)
The invention provides a method for preparing a sitagliptin intermediate, which comprises the following steps of: converting a compound 1 into a compound 2 at the reaction temperature of 55 to 80 DEGC by taking ethyl acetate as a reaction solvent under the protection of nitrogen and under an acidic condition to obtain turbid liquid containing the compound 2, wherein the ratio of the compound 1 toethyl acetate is controlled to be 1g:5-10ml. According to the present invention, with the method, the defects of the existing process are improved, the production efficiency is improved, the production cost is reduced, the good social benefits and the good economic benefits can be provided, and the economic value potential is large.
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.
Microwave-Assisted Synthesis and Antituberculosis Screening of Some 4-((3-(Trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-l)methyl)benzenamine Hybrids
Patil, Yogesh,Shingare, Ramesh,Choudhari, Amit,Sarkar, Dhiman,Madje, Balaji
, p. 434 - 442 (2019/01/04)
In the present investigation, a series of 4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)benzenamine analogs 6a–o were synthesized and characterized by IR, NMR (1H and 13C), and mass spectra. All newly synthesized compounds 6a–o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a–o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC50: 1.82?μg/mL), 6j (IC50: 1.02?μg/mL), and 6k (IC50: 1.59?μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC90 value of 16.02?μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M.?tuberculosis that can be explored further for the potential antitubercular drug.
Design, synthesis, biological evaluation and computational study of novel triazolo [4,3-a]pyrazin analogues
Jethava, Divya J.,Acharya, Prachi T.,Vasava, Mahesh S.,Bhoi, Manoj N.,Bhavsar, Zeel A.,Rathwa, Sanjay K.,Rajani, Dhanji P.,Patel, Hitesh D.
, p. 168 - 192 (2019/03/04)
The triazolo [4,3-a]pyrazin analogues are of interest due to their potential activity against various infectious and non-infectious disease. In search of suitable potent drug candidate, we report here the design, synthesis, characterization, biological activities and computation study of novel triazolo [4,3-a]pyrazin analogues. The synthesized molecules were characterized by various spectroscopic studies such as IR, Mass, 1H NMR, 13C NMR and elemental analysis. The newly synthesized compounds were evaluated for their in vitro biological activities such as anti-malarial, anti-tuberculosis, anti-bacterial and anti-fungal activities against plasmodium falciparum, H37Rv, various bacterial and fungal strains, respectively. The molecular docking study was carried out with enzyme aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum to analyze their binding orientation in the active site of the aspartic proteinase enzyme. The best docking complex was subjected to molecular dynamics simulation to illustrate the stability of these complexes and the most prominent interactions during the simulated trajectory. We have also calculated ADMET properties of all the synthesized compounds to predict the pharmacokinetic properties for the selection of the active and bioavailability of compounds.
PROCESS FOR THE PREPARATION OF TRIAZOLE AND SALT THEREOF
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Paragraph 0088; 0089; 0090; 0091; 0092; 0093; 0094; 0095, (2018/08/30)
An improved process for the preparation of Triazole and salts thereof, a key intermediate for the synthesis of Sitagliptine is disclosed.
Synthesis technology of Sitagliptin intermediate
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Paragraph 0031; 0032; 0034; 0036; 0038, (2018/06/26)
The invention discloses a synthesis technology of a Sitagliptin intermediate. The technology comprises specific steps as follows: a), in isopropanol, a compound 2 is converted into a Sitagliptin intermediate 1 in a certain temperature range under the acidic condition; b), a suspension containing the Sitagliptin intermediate 1 is obtained in isopropanol; c), in isopropanol, the Sitagliptin intermediate 1 is separated from the suspension containing the Sitagliptin intermediate 1 obtained in step b). Only one solvent, namely, isopropanol, is utilized in the whole synthesis technology, so that thesolvent dosage of the reaction process and product separation is reduced, meanwhile, introduction of other solvents in the whole technological process is prevented, and production efficiency is improved and the solvent is recycled while production is enlarged.
A west he row sandbank intermediate triazole and pyrazine derivatives of preparation method
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Paragraph 0052, (2017/08/25)
The invention relates to a preparation method of a sitagliptin intermediate triazolopyrazine derivative. The method comprises the following steps: by using 2-chlorethamin hydrochloride as an initial raw material, reacting the 2-chlorethamin hydrochloride with trifluoroacetate and aminoacetate hydrochloride to generate 1-trifluoroacetyl-2-piperazino ketone (III), and carrying out condensation ring formation on the compound (III), hydrazine hydrate and hydrochloric acid to obtain the sitagliptin intermediate 3-trifluoromethyl-5,6,7,8-tetrahydro-1,2,4-triazolyl[4,3-a]pyrazine hydrochloride (II). The high-activity triluoroacetyl carbonyl functional group and hydrazine hydrate are dehydrated into hydrazone, and the hydrochloric acid is directly added without separation, thereby performing intramolecular dehydration to generate the triazole ring. The method can avoid using thioketone, has the advantages of cheap and accessible raw materials, high reaction selectivity, short process, simple technical operation, high safety and environment friendliness.
