Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug Functionalization
Unsymmetrical urea derivatives are essential structural motifs in a wide array of biologically significant compounds. Despite the well-established methods for synthesizing symmetrical ureas, efficient strategies for the synthesis of unsymmetrical urea derivatives remain limited. In this study, we pr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/23/5669 |
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| author | Subban Kathiravan Prakriti Dhillon Tianshu Zhang Ian A. Nicholls |
| author_facet | Subban Kathiravan Prakriti Dhillon Tianshu Zhang Ian A. Nicholls |
| author_sort | Subban Kathiravan |
| collection | DOAJ |
| description | Unsymmetrical urea derivatives are essential structural motifs in a wide array of biologically significant compounds. Despite the well-established methods for synthesizing symmetrical ureas, efficient strategies for the synthesis of unsymmetrical urea derivatives remain limited. In this study, we present a novel approach for the synthesis of unsymmetrical urea derivatives through the coupling of amides and amines. Utilizing hypervalent iodine reagent PhI(OAc)<sub>2</sub> as a coupling mediator, this method circumvents the need for metal catalysts, high temperatures, and inert atmosphere. The reaction proceeds under mild conditions and demonstrates broad substrate scope, including various primary and secondary amines and primary benzamides. This protocol not only offers a practical and versatile route for synthesizing unsymmetrical ureas but also shows significant potential for the late-stage functionalization of complex molecules in drug development. |
| format | Article |
| id | doaj-art-e30096eae04b4606949402462ce89344 |
| institution | DOAJ |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-e30096eae04b4606949402462ce893442025-08-20T02:50:34ZengMDPI AGMolecules1420-30492024-11-012923566910.3390/molecules29235669Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug FunctionalizationSubban Kathiravan0Prakriti Dhillon1Tianshu Zhang2Ian A. Nicholls3Bioorganic & Biophysical Chemistry Laboratory, Linnaeus University Centre for Biomaterials Chemistry, Department of Chemistry & Biomedical Sciences, Linnaeus University, SE-39182 Kalmar, SwedenBioorganic & Biophysical Chemistry Laboratory, Linnaeus University Centre for Biomaterials Chemistry, Department of Chemistry & Biomedical Sciences, Linnaeus University, SE-39182 Kalmar, SwedenBioorganic & Biophysical Chemistry Laboratory, Linnaeus University Centre for Biomaterials Chemistry, Department of Chemistry & Biomedical Sciences, Linnaeus University, SE-39182 Kalmar, SwedenBioorganic & Biophysical Chemistry Laboratory, Linnaeus University Centre for Biomaterials Chemistry, Department of Chemistry & Biomedical Sciences, Linnaeus University, SE-39182 Kalmar, SwedenUnsymmetrical urea derivatives are essential structural motifs in a wide array of biologically significant compounds. Despite the well-established methods for synthesizing symmetrical ureas, efficient strategies for the synthesis of unsymmetrical urea derivatives remain limited. In this study, we present a novel approach for the synthesis of unsymmetrical urea derivatives through the coupling of amides and amines. Utilizing hypervalent iodine reagent PhI(OAc)<sub>2</sub> as a coupling mediator, this method circumvents the need for metal catalysts, high temperatures, and inert atmosphere. The reaction proceeds under mild conditions and demonstrates broad substrate scope, including various primary and secondary amines and primary benzamides. This protocol not only offers a practical and versatile route for synthesizing unsymmetrical ureas but also shows significant potential for the late-stage functionalization of complex molecules in drug development.https://www.mdpi.com/1420-3049/29/23/5669hypervalent iodineureaamidesamineslate-stage functionalizationdrugs |
| spellingShingle | Subban Kathiravan Prakriti Dhillon Tianshu Zhang Ian A. Nicholls Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug Functionalization Molecules hypervalent iodine urea amides amines late-stage functionalization drugs |
| title | Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug Functionalization |
| title_full | Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug Functionalization |
| title_fullStr | Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug Functionalization |
| title_full_unstemmed | Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug Functionalization |
| title_short | Synthesis of Unsymmetrical Urea Derivatives via PhI(OAc)<sub>2</sub> and Application in Late-Stage Drug Functionalization |
| title_sort | synthesis of unsymmetrical urea derivatives via phi oac sub 2 sub and application in late stage drug functionalization |
| topic | hypervalent iodine urea amides amines late-stage functionalization drugs |
| url | https://www.mdpi.com/1420-3049/29/23/5669 |
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