Multicomponent Reaction-Based Heteroannulations: A Direct Access to Fused Tetrazolo Piperazinones and 1,4-Diazepanones

Abstract

By exploiting the chemistry of bifunctional isocyanides, straightforward, rapid, and scalable Ugi-tetrazole-based multicomponent reaction heteroannulations were developed. Our synthetic approach provides a series of diverse fused tetrazolo piperazinones and 1,4-diazepanones in just one step.

Key words

isocyanides - tetrazoles - piperazinones - diazepanones - Ugi reaction - multicomponent reaction

Publication History

Received: 11 December 2023

Accepted after revision: 05 January 2024

Accepted Manuscript online:
05 January 2024

Article published online:
07 February 2024

• References and Notes

• 1 Dandapani S, Rosse G, Southall N, Salvino JM, Thomas CJ. Curr. Protoc. Chem. Biol. 2012; 4: 177
• 2 van Vlijmen H, Ortholand J.-Y, Li VM.-J, de Vlieger JS. B. Drug Discovery Today 2021; 26: 2406
• 3 Saha A, Varghese T, Liu A, Allen SJ, Mirzadegan T, Hack MD. J. Chem. Inf. Model. 2018; 58: 2057
• 4 Wigglesworth MJ, Murray DC, Blackett CJ, Kossenjans M, Nissink JW. M. Curr. Opin. Chem. Biol. 2015; 26: 104
• 5 Dahlin JL, Walters MA. Future Med. Chem. 2014; 6: 1265
• 6 Glick M, Jacoby E. Curr. Opin. Chem. Biol. 2011; 15: 540
• 7 Kerru N, Gummidi L, Maddila S, Gangu KK, Jonnalagadda SB. Molecules 2020; 25: 1909
• 8 Amin A, Qadir T, Sharma PK, Jeelani I, Abe H. Open Med. Chem. J. 2022; 16: e187410452209010
• 9 Procopiou PA, Ancliff RA, Bamford MJ, Browning C, Connor H, Davies S, Fogden YC, Hodgson ST, Holmes DS, Looker BE, Morriss KM. L, Parr CA, Pickup EA, Sehmi SS, White GV, Watts CJ, Wilson DM, Woodrow MD. J. Med. Chem. 2007; 50: 6706
• 10 Powell NA, Ciske FL, Clay EC, Cody WL, Downing DM, Blazecka PG, Holsworth DD, Edmunds JJ. Org. Lett. 2004; 6: 4069
• 11 El Kaim L, Gageat M, Gaultier L, Grimaud L. Synlett 2007; 500
• 12 Hulme C, Peng J, Louridas B, Menard P, Krolikowski P, Kumar NV. Tetrahedron Lett. 1998; 39: 8047
• 13 Hulme C, Cherrier M.-P. Tetrahedron Lett. 1999; 40: 5295
• 14 Hulme C, Ma L, Kumar NV, Krolikowski PH, Allen AC, Labaudiniere R. Tetrahedron Lett. 2000; 41: 1509
• 15 Abelman MM, Fisher KJ, Doerffler EM, Edwards PJ. Tetrahedron Lett. 2003; 44: 1823
• 16 Gellerman G, Hazan E, Kovaliov M, Albeck A, Shatzmiler S. Tetrahedron 2009; 65: 1389
• 17 Vaňková B, Brulíková L, Wu B, Krchňák V. Eur. J. Org. Chem. 2012; 5075
• 18 Ben Haj Salah K, Legrand B, Bibian M, Wenger E, Fehrentz J.-A, Denoyelle S. Org. Lett. 2018; 20: 3250
• 19 Wang W, Ollio S, Herdtweck E, Dömling A. J. Org. Chem. 2011; 76: 637
• 20 Pérez-Martín C, Rebolledo F, Brieva R. Adv. Synth. Catal. 2022; 364: 1326
• 21 Biftu T, Feng D, Qian X, Liang G.-B, Kieczykowski G, Eiermann G, He H, Leiting B, Lyons K, Petrov A, Sinha-Roy R, Zhang B, Scapin G, Patel S, Gao Y.-D, Singh S, Wu J, Zhang X, Thornberry NA, Weber AE. Bioorg. Med. Chem. Lett. 2007; 17: 49
• 22 Mravljak J, Monasson O, Al-Dabbagh B, Crouvoisier M, Bouhss A, Gravier-Pelletier C, Le Merrer Y. Eur. J. Med. Chem. 2011; 46: 1582
• 23 Gravier-Pelletier C, Charvet I, Le Merrer Y, Depezay J.-C. J. Carbohydr. Chem. 1997; 16: 129
• 24 Wang S, Wang S, Song S, Gao Q, Wen C, Zhang Z, Zheng L, Xiang J. J. Org. Chem. 2021; 86: 6458
• 25 Medda F, Martinez-Ariza G, Hulme C. Tetrahedron Lett. 2015; 56: 5295
• 26 Staniszewska M, Zdrojewski T, Gizińska M, Rogalska M, Kuryk Ł, Kowalkowska A, Łukowska-Chojnacka E. Eur. J. Med. Chem. 2022; 230: 114060
• 27 Farhid H, Khodkari V, Nazeri MT, Javanbakht S, Shaabani A. Org. Biomol. Chem. 2021; 19: 3318
• 28 Lecointre B, Narozny R, Borrello MT, Senger J, Chakrabarti A, Jung M, Marek M, Romier C, Melesina J, Sippl W, Bischoff L, Ganesan A. Philos. Trans. R. Soc., B 2018; 373: 20170364
• 29 Hulme C, Ma L, Cherrier M.-P, Romano JJ, Morton G, Duquenne C, Salvino J, Labaudiniere R. Tetrahedron Lett. 2000; 41: 1883
• 30 Shi L, Wen M, Li F. Chin. J. Chem. 2021; 39: 317
• 31 Heravi MM, Zadsirjan V. RSC Adv. 2020; 10: 44247
• 32 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 33 Neochoritis CG, Zhao T, Dömling A. Chem. Rev. 2019; 119: 1970
• 34 Nixey T, Kelly M, Hulme C. Tetrahedron Lett. 2000; 41: 8729
• 35 Akritopoulou-Zanze I, Gracias V, Djuric SW. Tetrahedron Lett. 2004; 45: 8439
• 36 Umkehrer M, Kolb J, Burdack C, Ross G, Hiller W. Tetrahedron Lett. 2004; 45: 6421
• 37 Hulme C, Morrissette MM, Volz FA, Burns CJ. Tetrahedron Lett. 1998; 39: 1113
• 38 Dömling A, Huang Y. Synthesis 2010; 2859
• 39 Gao L, Shaabani S, Reyes Romero A, Xu R, Ahmadianmoghaddam M, Dömling A. Green Chem. 2023; 25: 1380
• 40 Zarganes-Tzitzikas T, Patil P, Khoury K, Herdtweck E, Dömling A. Eur. J. Org. Chem. 2015; 2015: 51
• 41 Patil P, Kurpiewska K, Kalinowska-Tłuścik J, Dömling A. ACS Comb. Sci. 2017; 19: 343
• 42 Wang Y, Patil P, Kurpiewska K, Kalinowska-Tłuścik J, Dömling A. ACS Comb. Sci. 2017; 19: 193
• 43 Nixey T, Kelly M, Semin D, Hulme C. Tetrahedron Lett. 2002; 43: 3681
• 44 Nayak M, Batra S. Tetrahedron Lett. 2010; 51: 510
• 45 Borisov RS, Polyakov AI, Medvedeva LA, Khrustalev VN, Guranova NI, Voskressensky LG. Org. Lett. 2010; 12: 3894
• 46 Yerande SG, Newase KM, Singh B, Boltjes A, Dömling A. Tetrahedron Lett. 2014; 55: 3263
• 47 Fragkiadakis M, Anastasiou P.-K, Zingiridis M, Triantafyllou-Rundell ME, Reyes Romero A, Stoumpos CC, Neochoritis CG. J. Org. Chem. 2023; 88: 12709
• 48 Fragkiadakis M, Neochoritis CG. Synlett 2022; 33: 1913
• 49 Zarganes-Tzitzikas T, Chandgude AL, Dömling A. Chem. Rec. 2015; 15: 981
• 50 Lipinski CA. Drug Discovery Today: Technol. 2004; 1: 337
• 51 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Adv. Drug Delivery Rev. 2001; 46: 3
• 52 Ugi-Tetrazole Four-Component Synthesis of 10a–k; General Procedure The aldehyde (1.0 mmol) was added to a stirred solution of the amine (1.0 mmol) and Et₃N (1.0 mmol) in MeOH (1.0 mL), and the mixture was stirred for 10 min. The isocyanide 9 (1.0 mmol) and TMSN₃ (1.0 mmol) were then added, and the mixture was stirred vigorously for 48 h at 40 °C. The solvent was removed under reduced pressure, and the residue was purified by column chromatography [silica gel, PE–EtOAc (5:1 to 1:1)].
• 53 Ethyl 3-(4-Cyclopropyl-9-methyl-6-oxo-4H-tetrazolo[1,5-a]thieno[2,3-f][1,4]diazepin-5(6H)-yl)propanoate (10a) Yellow oil; yield: 157 mg (51%). ¹H NMR (500 MHz, CDCl₃): δ = 7.37–7.33 (d, J = 19.5 Hz, 1 H), 4.10–4.06 (m, 1 H), 3.70–3.68 (d, J = 7.5 Hz, 3 H), 3.64–3.61 (d, J = 12.9 Hz, 2 H), 3.15–3.12 (m, 1 H), 2.45–2.43 (m, 1 H), 2.34–2.30 (m, 1 H), 2.00–1.94 (d, J = 16.1 Hz, 3 H), 1.13–0.95 (m, 1 H), 0.63–0.47 (m, 1 H), 0.33–0.31 (m, 1 H), 0.15–0.13 (m, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 173.0, 160.1, 158.6, 157.8, 136.9, 134.1, 127.2, 60.5, 58.1, 52.7, 51.7, 43.0, 34.6, 15.6, 13.3, 4.3, 3.3, 2.9. HRMS (ESI): m/z [M + CH₃OH]⁺ calcd for C₁₇H₂₃N₅O₄S: 394.1514; found: 394.1547. Ethyl [8-(4-Chlorophenyl)-6-oxo-5,6-dihydrotetrazolo[1,5-a]pyrazin-7(8H)-yl]acetate (10i) Yellow oil; yield: 162 mg (57%). ¹H NMR (500 MHz, CDCl₃): δ = 7.42–7.40 (m, 2 H), 7.26–7.25 (m, 2 H), 6.13 (s, 1 H), 5.31–5.26 (m, 2 H), 4.75–4.71 (d, J = 17.5 Hz, 1 H), 4.19–4.17 (m, 2 H), 3.54–3.50 (d, J = 17.5 Hz, 1 H), 1.26–1.24 (m, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 167.6, 161.6, 149.6, 136.1, 132.9, 129.9, 128.9, 61.9, 57.3, 47.8, 45.9, 13.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₁₅ClN₅O₃: 336.0842; found: 336.0856.