Continuous flow synthesis of 3-thio-1,2,4-triazoles and biological evaluation
| Full text | |
| Author(s): |
Damiao, Mariana C. F. C. B.
[1]
;
Galaverna, Renan
[1]
;
Kozikowski, Alan P.
[2]
;
Eubanks, James
[3]
;
Pastre, Julio C.
[1]
Total Authors: 5
|
| Affiliation: | [1] Univ Campinas UNICAMP, Inst Chem, POB 6154, BR-13083970 Campinas, SP - Brazil
[2] StarWise Therapeut LLC, Univ Res Pk, Madison, WI 53719 - USA
[3] Krembil Res Inst, Div Genet & Dev, Toronto, ON M5T 2S8 - Canada
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | REACTION CHEMISTRY & ENGINEERING; v. 2, n. 6, p. 896-907, DEC 2017. |
| Web of Science Citations: | 3 |
| Abstract | |
We report herein the successful application of continuous flow micro reactors to prepare important building blocks based on the 3-thio-1,2,4-triazole core. A telescoped continuous flow process was developed based on the condensation of hydrazides and isothiocyanates to deliver an in situ stream of a thiosemicarbazide, which subsequently was cyclized under basic conditions. The obtained 1,2,4-triazole-3-thiol was further alkylated with benzyl/alkyl halides. In addition, we evaluated the scope of heterocycle formation and alkylation using different hydrazides, isothiocyanates, and aryl/alkyl chlorides, bromides and iodides. We were able to synthesize a small library of 18 compounds in 48 minutes of residence time for each synthesis, and in moderate to excellent yields, in a telescoped fashion. The fully integrated synthesis flow platform enables the fast generation of compound libraries, reducing the time consumed in preliminary stages of a drug discovery process. (AU) | |
| FAPESP's process: | 13/07607-8 - OCRC - Obesity and Comorbidities Research Center |
| Grantee: | Licio Augusto Velloso |
| Support type: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 15/18572-6 - Continuous flow synthesis of 3-thio-1,2,4-triazoles and biological evaluation |
| Grantee: | Mariana Celestina Frojuello Costa Bernstorff Damião |
| Support type: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 14/25770-6 - New frontiers in cross-coupling reactions promoted by palladium: combining enantioselective catalysis, C-H activations, new materials and in flux reactions aiming at high efficiency and sustainability in synthetic processes |
| Grantee: | Carlos Roque Duarte Correia |
| Support type: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/26378-2 - Development of methodologies and synthetic processes employing a new technological platform: micro and meso reactor assisted synthesis of natural products and derivatives with potential pharmacological activity |
| Grantee: | Júlio Cezar Pastre |
| Support type: | Research Grants - Young Investigators Grants |