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2000
Volume 22, Issue 8
  • ISSN: 1570-1786
  • E-ISSN: 1875-6255

Abstract

The ureido moiety stands as one of the most regarded scaffolds in medicinal and organic synthesis. In this study, we endeavored to synthesize a product containing tertiary amine moieties through the nucleophilic substitution reaction of the 2-chloroethyl urea derivative with a secondary amine, utilizing either inorganic bases, such as KCO or organic bases like triethylamine as acid-binding agents in diverse reaction media. Unfortunately, the reaction failed to yield the desired nucleophilic substitution product in high yield, attributed to the reactivity of the 2-chloroethyl urea derivative. The structures of potential impurities were elucidated based on comprehensive spectroscopic data, including 1H NMR, 13C NMR, HRMS, HMBC, and HSQC.

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References

  1. GhoshA.K. BrindisiM. J. Med. Chem.20206362751278810.1021/acs.jmedchem.9b01541 31789518
     [Google Scholar]
  2. VaniB.P. AranganathanA. TiwaryP. J. Chem. Inf. Model.20246472789279710.1021/acs.jcim.3c01436 37981824
     [Google Scholar]
  3. VaisarD. AhnN.G. Curr. Opin. Struct. Biol.20248910293510.1016/j.sbi.2024.102935 39395271
     [Google Scholar]
  4. HerringtonN.B. LiY.C. SteinD. PandeyG. SchlessingerA. PLOS Comput. Biol.2024207e101230210.1371/journal.pcbi.1012302 39046952
     [Google Scholar]
  5. ListroR. RossinoG. PiaggiF. SonekanF.F. RossiD. LincianoP. CollinaS. Front Chem.20221099535110.3389/fchem.2022.995351 36186578
     [Google Scholar]
  6. RohillaJ. MishraR. VarshneyS. MazumderA. MazumderR. KumarA. KaurA. Curr. Org. Chem.202428171366137910.2174/0113852728307286240517054021
     [Google Scholar]
  7. Pratap Reddy GajulapalliV. ChemMedChem20231819e20220069310.1002/cmdc.202200693 37442809
     [Google Scholar]
  8. KumarR. GoelH. SolankiR. RawatL. TabasumS. TanwarP. PalS. SabarwalA. Med. Drug. Discov.20242310019510.1016/j.medidd.2024.100195 39281823
     [Google Scholar]
  9. OuelletteV. BouzribaC. Chavez AlvarezA.C. Hamel-CôtéG. FortinS. Bioorg. Med. Chem. Lett.202410512974510.1016/j.bmcl.2024.129745 38614151
     [Google Scholar]
  10. OuelletteV. Chavez AlvarezA.C. BouzribaC. Hamel-CôtéG. FortinS. Bioorg. Chem.202314010682010.1016/j.bioorg.2023.106820 37672952
     [Google Scholar]
  11. BouchonB. ChambonC. MounetouE. PaponJ. Miot-NoiraultE. GaudreaultR.C. MadelmontJ.C. DegoulF. Mol. Pharmacol.20056851415142210.1124/mol.105.015586 16099845
     [Google Scholar]
  12. JordanM.A. WilsonL. Nat. Rev. Cancer20044425326510.1038/nrc1317 15057285
     [Google Scholar]
  13. LiH.-Q. LvP.-C. YanT. ZhuH.-L. Anticancer. Agents Med. Chem.2009101110.2174/1871520611009010001 20235348
     [Google Scholar]
  14. ZhongH. BowenJ. Curr. Med. Chem.200613884986210.2174/092986706776361085 16611071
     [Google Scholar]
  15. PetitclercE. DeschesnesR.G. CôtéM-F. MarquisC. JanvierR. LacroixJ. Miot-NoiraultE. LegaultJ. MounetouE. MadelmontJ-C. C -GaudreaultR. Cancer Res.200464134654466310.1158/0008‑5472.CAN‑03‑3715 15231678
     [Google Scholar]
  16. PatenaudeA. FortinJ.S. DeschenesR. CoteM-F. LacroixJ. Can. J. Physiol. Pharmacol.201088111102111410.1139/Y10‑084 21076498
     [Google Scholar]
  17. BouchonB. PaponJ. CommunalY. MadelmontJ-C. DegoulF. Br. J. Pharmacol.2007152444945510.1038/sj.bjp.0707415 17704829
     [Google Scholar]
  18. UeckerM. da SilvaR. GramppT. PaschT. SchaubM.C. ZauggM. Anesthesiology200399113814710.1097/00000542‑200307000‑00023 12826853
     [Google Scholar]
  19. PatenaudeA. DeschesnesR.G. RousseauJ.L. PetitclercE. LacroixJ. CôtéM-F. C-GaudreaultR. Cancer Res.20076752306231610.1158/0008‑5472.CAN‑06‑3824 17332362
     [Google Scholar]
  20. RakovicA. GrünewaldA. VogesL. HofmannS. OrolickiS. LohmannK. KleinC. Parkinsons Dis.2011201111910.4061/2011/153979 21437181
     [Google Scholar]
  21. JapB.K. WalianP.J. Physiol. Rev.19967641073108810.1152/physrev.1996.76.4.1073 8874494
     [Google Scholar]
  22. XiaoF. JiangH. LiZ. JiangX. ChenS. NiuY. YinH. ShuY. PengB. LuW. LiX. LiZ. LanS. XuX. GuoF. Nat. Commun.2023141252310.1038/s41467‑023‑38141‑0 37130842
     [Google Scholar]
  23. MistryS.N. BakerJ.G. FischerP.M. HillS.J. GardinerS.M. KellamB. J. Med. Chem.201356103852386510.1021/jm400348g 23614528
     [Google Scholar]
  24. HwangS.H. MorisseauC. DoZ. HammockB.D. Bioorg. Med. Chem. Lett.200616225773577710.1016/j.bmcl.2006.08.078 16949285
     [Google Scholar]
  25. ErhardtP.W. WooC.M. MatierW.L. GorczynskiR.J. AndersonW.G. J. Med. Chem.19832681109111210.1021/jm00362a004 6135805
     [Google Scholar]
  26. LimV.J.Y. ProudmanR.G.W. MonteleoneS. KolbP. BakerJ.G. Mol. Pharmacol.20231032899910.1124/molpharm.122.000583 36351797
     [Google Scholar]
  27. RüütelA. TshepelevitshS. LeitoI. J. Org. Chem.20228721141861419310.1021/acs.joc.2c01725 36214741
     [Google Scholar]
  28. AnbarH.S. El-GamalM.I. TaraziH. LeeB.S. JeonH.R. KwonD. OhC.H. J. Enzyme Inhib. Med. Chem.20203511712172610.1080/14756366.2020.1819260 32962435
     [Google Scholar]
  29. ZhanW. VisoneJ. OuelletteT. HarrisJ.C. WangR. ZhangH. SinghP.K. GinnJ. SukenickG. WongT.T. OkoroJ.I. ScalesR.M. TumwebazeP.K. RosenthalP.J. KafsackB.F.C. CooperR.A. MeinkeP.T. KirkmanL.A. LinG. J. Med. Chem.201962136137614510.1021/acs.jmedchem.9b00363 31177777
     [Google Scholar]
  30. El-DinM.M.G. El-GamalM.I. Abdel-MaksoudM.S. YooK.H. OhC-H. Eur. J. Med. Chem.201611912213110.1016/j.ejmech.2016.04.048 27155467
     [Google Scholar]
  31. MejdrováI. ChalupskáD. KöglerM. ŠálaM. PlačkováP. BaumlováA. HřebabeckýH. ProcházkováE. DejmekM. GuillonR. StruninD. WeberJ. LeeG. BirkusG. Mertlíková-KaiserováH. BouraE. NenckaR. J. Med. Chem.20155893767379310.1021/acs.jmedchem.5b00499 25897704
     [Google Scholar]
  32. PagireS.H. PagireH.S. LeeG.B. HanS-J. KwakH.J. KimJ.Y. KimK.Y. Dal RheeS. Eur. J. Med. Chem.201510171673510.1016/j.ejmech.2015.06.043 26218650
     [Google Scholar]
  33. Beena and RawatD.S. Med. Res. Rev.201333469376410.1002/med.21262 22622957
     [Google Scholar]
  34. LallemandB. ChaixF. BuryM. BruyèreC. GhostinJ. BeckerJ-P. DelporteC. GelbckeM. MathieuV. DuboisJ. PrévostM. JabinI. KissR. J. Med. Chem.201154196501651310.1021/jm200285z 21888390
     [Google Scholar]
  35. ParkJ.H. El-GamalM.I. LeeY.S. OhC.H. Eur. J. Med. Chem.201146125769577710.1016/j.ejmech.2011.08.024 22033063
     [Google Scholar]
  36. RamiH.K. ThompsonM. WymanP. JermanJ.C. EgertonJ. BroughS. StevensA.J. RandallA.D. SmartD. GunthorpeM.J. DavisJ.B. Bioorg. Med. Chem. Lett.200414143631363410.1016/j.bmcl.2004.05.028 15203132
     [Google Scholar]
  37. ZhuK. WangL. LiaoT. LiW. ZhouJ. YouY. ShiJ. Eur. J. Med. Chem.202326111580610.1016/j.ejmech.2023.115806 37713804
     [Google Scholar]
  38. Aghazadeh TabriziM. BaraldiP.G. BaraldiS. GessiS. MerighiS. BoreaP.A. Med. Res. Rev.201737493698310.1002/med.21427 27976413
     [Google Scholar]
  39. KymP.R. KortM.E. HutchinsC.W. Biochem. Pharmacol.200978321121610.1016/j.bcp.2009.02.014 19481638
     [Google Scholar]
  40. SzallasiA. GunthorpeM. Curr. Pharm. Des.2008141324110.2174/138161208783330754 18220816
     [Google Scholar]
  41. MishraC.B. KumariS. AngeliA. MontiS.M. BuonannoM. TiwariM. SupuranC.T. J. Med. Chem.20176062456246910.1021/acs.jmedchem.6b01804 28253618
     [Google Scholar]
  42. SethiK.K. VermaS.M. TançM. PurperG. CalafatoG. CartaF. SupuranC.T. Bioorg. Med. Chem.20142251586159510.1016/j.bmc.2014.01.031 24513184
     [Google Scholar]
  43. El-AzabA.S. A-M Abdel-AzizA. BuaS. NocentiniA. BakheitA.H. AlkahtaniH.M. HefnawyM.M. SupuranC.T. Saudi Pharm. J.2023311210186610.1016/j.jsps.2023.101866 38033749
     [Google Scholar]
  44. BuemiM.R. Di FioreA. De LucaL. AngeliA. MancusoF. FerroS. MontiS.M. BuonannoM. RussoE. De SarroG. De SimoneG. SupuranC.T. GittoR. Eur. J. Med. Chem.201916344345210.1016/j.ejmech.2018.11.073 30530195
     [Google Scholar]
  45. OudahK.H. MahmoudW.R. AwadallahF.M. TaherA.T. AbbasS.E.S. AllamH.A. VulloD. SupuranC.T. J. Enzyme Inhib. Med. Chem.2023381122310.1080/14756366.2022.2132485 36305274
     [Google Scholar]
  46. MoiD. NocentiniA. DeplanoA. OsmanS.M. AlOthmanZ.A. PirasV. BalboniG. SupuranC.T. OnnisV. Bioorg. Chem.20209810372810.1016/j.bioorg.2020.103728 32182519
     [Google Scholar]
  47. WangY. GuoH. TangG. HeQ. ZhangY. HuY. WangY. LinZ. Comput. Biol. Chem.20198023424310.1016/j.compbiolchem.2019.03.005 31009872
     [Google Scholar]
  48. GiordanettoF. WållbergA. KnerrL. SelmiN. UllahV. ThorstenssonF. LindelöfÅ. KarlssonS. NikitidisG. LlinasA. WangQ.D. LindqvistA. HögbergÅ. LindhardtE. ÅstrandA. DukerG. Bioorg. Med. Chem. Lett.201323111912410.1016/j.bmcl.2012.10.140 23200256
     [Google Scholar]
  49. PittalàV. SiracusaM.A. ModicaM.N. SalernoL. PedrettiA. VistoliG. CagnottoA. MenniniT. RomeoG. Bioorg. Med. Chem.201119175260527610.1016/j.bmc.2011.06.043 21802308
     [Google Scholar]
  50. Carreira-BarralI. Fernández-PérezI. Mato-IglesiasM. De BlasA. Platas-IglesiasC. Esteban-GómezD. Molecules201823247910.3390/molecules23020479 29470445
     [Google Scholar]
  51. Carreira-BarralI. Riopedre-FernándezM. de BlasA. MosqueraJ. VázquezM.E. Platas-IglesiasC. Esteban-GómezD. J. Inorg. Biochem.202020511099510.1016/j.jinorgbio.2020.110995 31955057
     [Google Scholar]
  52. SobańskaA.W. ŻydekG. WłodnoP. BrzezińskaE. Eur. J. Med. Chem.20158914715510.1016/j.ejmech.2014.10.045 25462235
     [Google Scholar]
  53. EloyF. MousseboisC. Bull. Soc. Chim. Belg.1959687-942343110.1002/bscb.19590680701
     [Google Scholar]
  54. TheodoridisG. Tetrahedron Lett.199839519365936810.1016/S0040‑4039(98)02111‑X
     [Google Scholar]
  55. BuchmanR. ScozzieJ.A. AriyanZ.S. HeilmanR.D. RippinD.J. PyneW.J. PowersL.J. MatthewsR.J. J. Med. Chem.198023121398140510.1021/jm00186a021 7452694
     [Google Scholar]
  56. JonesC.D. Kershaw CookL.J. Marquez-GamezD. LuzyaninK.V. SteedJ.W. SlaterA.G. J. Am. Chem. Soc.2021143197553756510.1021/jacs.1c02891 33961419
     [Google Scholar]
  57. CusackK.P. ArgiriadiM.A. GordonT.D. HarrisC.M. HeroldJ.M. HoemannM.Z. YestrepskyB.D. Bioorg. Med. Chem. Lett.20237912904710.1016/j.bmcl.2022.129047 36400288
     [Google Scholar]
  58. ChengJ. QinJ. GuoS. QiuH. ZhongY. Bioorg. Med. Chem. Lett.201424194768477210.1016/j.bmcl.2014.06.080 25182565
     [Google Scholar]
  59. WangL. ZhangB. JiJ. LiB. YanJ. ZhangW. WuY. WangX. Eur. J. Med. Chem.20094483318332210.1016/j.ejmech.2009.03.021 19375196
     [Google Scholar]
  60. ClaydenJ. TurnerH. PickworthM. AdlerT. Org. Lett.20057153147315010.1021/ol0508025 16018607
     [Google Scholar]
  61. AdlerT. BonjochJ. ClaydenJ. Font-BardíaM. PickworthM. SolansX. SoléD. VallverdúL. Org. Biomol. Chem.20053173173318310.1039/b507202f 16106298
     [Google Scholar]
  62. LiX. XieM. LuC. MaoJ. CaoY. YangY. WeiY. LiuX. CaoS. SongY. PengJ. ZhouY. JiangQ. LinG. QinS. QiM. HouM. LiuX. ZhouH. YangG. YangC. Eur. J. Med. Chem.202020311261410.1016/j.ejmech.2020.112614 32679453
     [Google Scholar]
  63. BrogginiG. BarberaV. BeccalliE.M. ChiacchioU. FasanaA. GalliS. GazzolaS. Adv. Synth. Catal.201335581640164810.1002/adsc.201300104
     [Google Scholar]
  64. PokhvisnevaG.V. GordeevP.B. NikitinS.V. SmirnovG.A. TernikovaT.V. Luk’yanovO.A. Russ. Chem. Bull.20186791655166110.1007/s11172‑018‑2273‑6
     [Google Scholar]
  65. SalvatiM.E. MoranE.J. ArmstrongR.W. Tetrahedron Lett.199233263711371410.1016/0040‑4039(92)80005‑5
     [Google Scholar]
  66. NakaiK. YokoyaM. SaitoN. Chem. Pharm. Bull. (Tokyo)201361885386910.1248/cpb.c13‑00361 23902868
     [Google Scholar]
  67. ScutaruA.M. WenzelM. SchefflerH. WolberG. GustR. Bioconjug. Chem.201021101728174310.1021/bc900453f 20849062
     [Google Scholar]
  68. ChandraB. Sinha RoyK. ShaikM. WaghmareC. PalitM. Rapid Commun. Mass Spectrom.2020343e858610.1002/rcm.8586 31509283
     [Google Scholar]
  69. FortinS. WeiL. MoreauE. LacroixJ. CôtéM-F. PetitclercE. KotraL.P. C-GaudreaultR. J. Med. Chem.201154134559458010.1021/jm200488a 21604746
     [Google Scholar]
  70. FormentínP. GimenoN. SteinkeJ.H.G. VilarR. J. Org. Chem.200570208235823810.1021/jo051120y 16277358
     [Google Scholar]
  71. DoebelinC. SchmittM. AntheaumeC. BourguignonJ.J. BihelF. J. Org. Chem.20137822113351134110.1021/jo401738f 24090234
     [Google Scholar]
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Chemoselectivity Profiling in the Alkylation of 2-Chloroethylurea Derivatives with Secondary Amines
Lett. Org. Chem. 22, 633 (2025); https://doi.org/10.2174/0115701786357824250117052847
/content/journals/loc/10.2174/0115701786357824250117052847
/content/journals/loc/10.2174/0115701786357824250117052847
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  • Article Type:     Research Article
Keyword(s): 2-chloroethyl urea derivative; alkylation; chemoselectivity; impurities; nucleophilic substitution; secondary amines

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