Synlett 2024; 35(15): 1828-1832
letter
14th EuCheMS Young Investigators Workshop
Multicomponent Reaction-Based Heteroannulations: A Direct Access to Fused Tetrazolo Piperazinones and 1,4-Diazepanones
Eirini Fotopoulou
,
Alexandros Vasilakis
,
Financial support from The Hellenic Foundation for Research and Innovation (H.F.R.I.), under the ‘2nd Call for H.F.R.I. Research Projects to Support Post-Doctoral Researchers’ (Project Number: 0911), and from Empeirikeion Idryma is gratefully acknowledged.
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
Supporting Information
Supporting information for this article is available online at https://doi.org/10.1055/a-2239-6897.
Supporting Information
Publication History
Received: 11 December 2023
© 2024. Thieme. All rights reserved
Georg Thieme Verlag KG
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 Et3 N (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%). 1 H 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). 13 C 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 + CH3 OH]+ calcd for C17 H23 N5 O4 S: 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%). 1 H 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). 13 C 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 C14 H15 ClN5 O3 : 336.0842; found: 336.0856.
