Synlett 2018; 29(08): 1095-1101
DOI: 10.1055/s-0036-1591531
letter
© Georg Thieme Verlag Stuttgart · New York

Catalyst-Free Synthesis of Fused Triazolo-Diazepino[5,6-b]Quinoline Derivatives via a Sequential Ugi-4CR–Nucleophilic Substitution–Intramolecular Click Reaction

Saeed Balalaie*
a  Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran   Email: balalaie@kntu.ac.ir
b  Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
,
Aref Vaezghaemi
a  Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran   Email: balalaie@kntu.ac.ir
,
Nahid Zarezadeh
a  Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran   Email: balalaie@kntu.ac.ir
,
Frank Rominger
c  Organisch-Chemisches Institut der Universitaet Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
,
Hamid Reza Bijanzadeh
d  Department of Biophysics, Tarbiat Modares University, Tehran, Iran
› Author Affiliations
S. B. thanks the Alexander von Humboldt foundation for a Research Fellowship, the Iran National Science Foundation (INSF, Grant No. 96003234), and the National Institute for Medical Research Development (NIMAD) (Project No. 943185) for their financial support.
Further Information

Publication History

Received: 01 December 2017

Accepted after revision: 19 December 2017

Publication Date:
29 January 2018 (online)


Dedicated to Prof. Lutz Tietze on the occasion of his 75th birthday

Abstract

A convenient, post-transformational reaction has been ­developed for the construction of highly diversified quinoline-fused triazolo-diazepinones featuring four diversification points by employing a catalyst-free Ugi four-component–nucleophilic substitution–intra­molecular click cycloaddition sequence. This approach provides a wide scope of products with good yields and high bond-forming efficiency.

Supporting Information

 
  • References and Notes

    • 1a Dömling A. Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
    • 1b Nair V. Rajesh C. Vinod A. Bindu S. Sreekanth A. Mathen J. Balagopal L. Acc. Chem. Res. 2003; 36: 899
    • 1c Dömling A. Chem. Rev. 2006; 106: 17
    • 1d Orru RV. Ruijter E. Synthesis of Heterocycles via Multicomponent Reactions I. Springer; Berlin: 2010
    • 1e Dömling A. Wang W. Wang K. Chem. Rev. 2012; 112: 3083
    • 1f Rotstein BH. Zaretsky S. Rai V. Yudin AK. Chem. Rev. 2014; 114: 8323
  • 2 Marcaccini S. Torroba T. Nat. Protoc. 2007; 2: 632
  • 3 Zhu J. Bienayme H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2005
    • 4a Sharma UK. Sharma N. Vachhani DD. Van der Eycken EV. Chem. Soc. Rev. 2015; 44: 1836
    • 4b Cheng G. He X. Tian L. Chen J. Li C. Jia X. Li J. J. Org. Chem. 2015; 80: 11100
    • 4c Zeng X.-H. Wang H.-M. Ding M.-W. Org. Lett. 2015; 17: 2234
    • 4d Azuaje J. Pérez-Rubio JM. Yaziji V. El Maatougui A. González-Gomez JC. Sánchez-Pedregal VM. Navarro-Vázquez A. Masaguer CF. Teijeira M. Sotelo E. J. Org. Chem. 2015; 80: 1533
    • 4e Shi J. Wu J. Cui C. Dai W.-M. J. Org. Chem. 2016; 81: 10392
    • 4f Li Z. Zhao Y. Tian G. He Y. Song G. Van Meervelt L. Van der Eycken EV. RSC Adv. 2016; 6: 103601
    • 4g Ramanivas T. Parameshwar M. Gayatri G. Nanubolu JB. Srivastava AK. Eur. J. Org. Chem. 2017; 2245
  • 5 Evans BE. Bock MG. Rittle KE. DiPardo RM. Whitter WL. Veber DF. Anderson PS. Freidinger RM. Proc. Natl. Acad. Sci. U.S.A. 1986; 83: 4918
    • 6a Olkkola K. Ahonen J. Modern Anesthetics . Schüttler J. Schwilden J. Springer; Berlin: 2008: 335
    • 6b Hurley LH. Reck T. Thurston DE. Langley DR. Holden KG. Hertzberg RP. Hoover JR. Gallagher GJr. Faucette LF. Chem. Res. Toxicol. 1988; 1: 258
    • 7a Watanabe M. Maemura K. Kanbara K. Tamayama T. Hayasaki H. Int. Rev. Cytol. 2002; 213: 1
    • 7b Hanson SM. Czajkowski C. J. Neurosci. 2008; 28: 3490
    • 8a Smith SG. Sanchez R. Zhou M.-M. Chem. Biol. 2014; 21: 573
    • 8b Zhang G. Smith SG. Zhou M.-M. Chem. Rev. 2015; 115: 11625
    • 8c Filippakopoulos P. Knapp S. Nat. Rev. Drug Discovery 2014; 13: 337
  • 9 Filippakopoulos P. Qi J. Picaud S. Shen Y. Smith WB. Fedorov O. Morse EM. Keates T. Hickman TT. Felletar I. Nature 2010; 468: 1067
    • 10a Majumdar K. Ray K. Ganai S. Ghosh T. Synthesis 2010; 858
    • 10b Chowdhury C. Sasmal AK. Achari B. Org. Biomol. Chem. 2010; 8: 4971
    • 10c Chambers CS. Patel N. Hemming K. Tetrahedron Lett. 2010; 51: 4859
    • 10d Majumdar K. Ganai S. Synthesis 2013; 45: 2619
    • 10e Nguyen HH. Palazzo TA. Kurth MJ. Org. Lett. 2013; 15: 4492
    • 10f Hussain MK. Ansari MI. Kant R. Hajela K. Org. Lett. 2014; 16: 560
    • 10g Chen W. Li H. Gu X. Zhu Y. Synlett 2015; 26: 785
    • 10h Sudhapriya N. Nandakumar A. Arun Y. Perumal P. Balachandran C. Emi N. RSC Adv. 2015; 5: 66260
    • 10i Zhang X. Zhi S. Wang W. Liu S. Jasinski JP. Zhang W. Green Chem. 2016; 18: 2642
  • 11 Vachhani DD. Kumar A. Modha SG. Sharma SK. Parmar VS. Van der Eycken EV. Eur. J. Org. Chem. 2013; 1223
  • 12 Ruijter E. Scheffelaar R. Orru RV. Angew. Chem. Int. Ed. 2011; 50: 6234
    • 13a Makawana JA. Sangani CB. Lin L. Zhu H.-L. Bioorg. Med. Chem. Lett. 2014; 24: 1734
    • 13b Ghandi M. Zarezadeh N. Abbasi A. Org. Biomol. Chem. 2015; 13: 8211
    • 13c Mishra K. Pandey AK. Singh JB. Singh RM. Org. Biomol. Chem. 2016; 14: 6328
    • 13d Li K. Ou J. Gao S. Angew. Chem. Int. Ed. 2016; 128: 14778
  • 14 Wang H.-J. Camara F. Haber JC. Mangette JE. Tetrahedron Lett. 2015; 56: 1030
  • 15 Singh V. Hutait S. Batra S. Eur. J. Org. Chem. 2009; 3454
  • 16 An Y. He H. Liu T. Zhang Y. Lu X. Cai Q. Synthesis 2017; 49: 3863
    • 17a Bararjanian M. Balalaie S. Movassagh B. Bijanzadeh HR. Tetrahedron Lett. 2010; 51: 3277
    • 17b Bararjanian M. Balalaie S. Rominger F. Movassagh B. Bijanzadeh HR. J. Org. Chem. 2010; 75: 2806
    • 17c Maghari S. Ramezanpour S. Balalaie S. Darvish F. Rominger F. Bijanzadeh HR. J. Org. Chem. 2013; 78: 6450
    • 17d Ghabraie E. Balalaie S. Mehrparvar S. Rominger F. J. Org. Chem. 2014; 79: 7926
    • 17e Balalaie S. Shamakli M. Nikbakht A. Alavijeh NS. Rominger F. Rostamizadeh S. Bijanzadeh HR. Org. Biomol. Chem. 2017; 15: 5737
    • 17f Balalaie S. Mirzaie S. Nikbakht A. Hamdan F. Rominger F. Navari R. Bijanzadeh HR. Org. Lett. 2017; 19: 6124
    • 17g Balalaie S. RamezaniKejani R. Ghabraie E. Darvish F. Rominger F. Hamdan F. Bijanzadeh HR. J. Org. Chem. 2017; 82: 12141
    • 18a Baruah B. Bhuyan PJ. Tetrahedron 2009; 65: 7099
    • 18b Wang G.-B. Wang L.-F. Li C.-Z. Sun J. Zhou G.-M. Yang D.-C. Res. Chem. Intermed. 2012; 38: 77
    • 19a Balalaie S. Bararjanian M. Hosseinzadeh S. Rominger F. Bijanzadeh HR. Wolf E. Tetrahedron 2011; 67: 7294
    • 19b Ma D. Cai Q. Acc. Chem. Res. 2008; 41: 1450
  • 20 CCDC 1578505 contains the supplementary crystallographic data for 6o. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 21 Thomann A. Zapp J. Hutter M. Empting M. Hartmann R. Org. Biomol. Chem. 2015; 13: 10620
  • 22 Procedure for the Synthesis of 5a To a solution of 2-chloro-3-formylquinoline (1a, 191 mg, 1 mmol) in MeOH (5 mL), benzylamine (2a, 0.132 mL, 1 mmol), phenylpropynoic acid (3a, 146 mg, 1 mmol), and cyclohexyl isocyanide (4a, 0.124 mL, 1 mmol) were added, respectively. The solution was stirred for 24 h at r.t. with reaction progress being monitored by TLC. After completion of reaction, the colorless solid was filtered and washed with EtOH to yield the Ugi product 5a (0.477 g, yield 89%). N-Benzyl-N-[1-(2-chloroquinolin-3-yl)-2-(cyclohexylamino)-2-oxoethyl]-3-phenylpropiolamide (5a) Rotamer ratio = 77:23; colorless solid (0.509 g, 95%); mp 202–204 °C. IR (KBr): νmax = 3290 (NH), 2210 (C≡C), 1624 (C=O) cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.05–1.90 (m, 10 H, 5 CH2 of cyclohexyl), 3.73–3.87 (m, 1 H, CHNH of cyclohexyl), 4.64 (d, J = 15.2 Hz, 1 H, CH2Ph of minor rotamer), 4.80–4.91 (m, 1 H, CH2Ph of minor and major rotamer), 5.28 (d, J = 16.5 Hz, 1 H, CH2Ph of major rotamer), 6.36 (s, 1 H, CH of major rotamer), 6.41 (d, J = 8.0 Hz, 1 H, NH of minor rotamer), 6.54 (s, 1 H, CH of minor rotamer), 6.71 (d, J = 7.9 Hz, 1 H, NH of major rotamer), 6.91–7.04 (m, 5.2 H, Ar), 7.25–7.40 (m, 5 H, Ar), 7.51–7.57 (m, 1.5 H, Ar), 7.65–7.70 (m, 1 H, Ar), 7.79–7.84 (m, 2 H, Ar), 8.10 (s, 1 H, Ar of minor rotamer), 8.46 (s, 1 H, Ar of major rotamer) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.7, 25.4, 32.6, 48.9, 51.7, 58.3, 81.8 (C≡C of alkyne), 91.7 (C≡C of alkyne), 119.7, 119.9, 126.7, 126.8, 127.2, 127.3, 127.5, 127.8, 128.0, 128.1, 128.3, 128.5, 128.6, 130.3, 131.1, 132.5, 136.3, 137.0, 140.1, 147.0, 150.9, 155.9 (C=O), 156.4(C=O), 166.6 (C=O), 167.0 (C=O) ppm. General Procedure for the Synthesis of 6a–o To a solution of aldehyde 1a,b (1 mmol) in MeOH (5 mL), amine 2ac (1 mmol), acid 3a,b (1 mmol), and isocyanide 4a,b (1 mmol) were added, respectively. The solution was stirred for 24 h at r.t. After completion of the reaction, solvent was removed under reduced pressure and subsequently dissolved in DMF (3 mL). Sodium azide (1.5 mmol) was added to the mixture, the reaction vessel was evacuated and backfilled with argon, sealed and heated at 120 °C for 6 h. Reaction progress was monitored by TLC. After completion of reaction, the mixture was cooled to r.t., and then water (5 mL) was added, and the mixture was extracted with EtOAc (3 × 10 mL). The combined organic phases were dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by column chromatography using n-hexane/EtOAc (1:1) as eluent. 5-Benzyl-N-cyclohexyl-4-oxo-3-phenyl-5,6-dihydro-4H-[1,2,3]triazolo[5′,1′:3,4][1,4]diazepino[5,6-b]quinoline-6-carboxamide (6a) Pale yellow solid (0.439 g, 81%); mp 187–189 °C. IR (KBr): νmax = 3382 (NH), 1657 (C=O) cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.43–1.36 (m, 10 H, 5 CH2 of cyclohexyl), 3.23–3.33 (m, 1 H, CHNH of cyclohexyl), 4.96 (AB-q, J = 14.4 Hz, 2 H, CH2Ph), 5.18 (s, 1 H, CH), 5.34 (d, J = 7.7 Hz, 1 H, NH), 7.26–7.34 (m, 5 H, Ar), 7.39–7.53 (m, 4 H, Ar), 7.62 (d, J = 7.8 Hz, 1 H, Ar), 7.69 (s, 1 H, Ar), 7.73 (t, J = 7.1 Hz, 1 H, Ar), 8.03–8.09 (m, 3 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.5, 24.6, 25.0, 32.0, 32.3 (5 CH2 of cyclohexyl), 49.4 (CH2Ph), 51.8 (CHNH of cyclohexyl), 62.6 (CH), 123.3, 127.5, 127.6, 127.7, 128.4, 128.6, 128.7, 129.2 (2 C), 129.3, 129.4, 129.5, 131.7, 135.5, 139.9, 140.0, 144.8, 146.8, 150.1, 158.9 (C=O), 164.7 (C=O) ppm. HRMS (ESI): m/z calcd for C33H31N6O2 [M + H]+: 543.2503; found: 543.2510; m/z calcd for C33H30N6NaO2 [M + Na]+: 565.2322; found: 565.2326; m/z calcd for C33H30KN6O2 [M + K]+: 581.2062; found: 581.2070; m/z calcd for C66H61N12O4 [2M + H]+: 1085.4933; found: 1085.4959; m/z calcd for C66H60N12NaO4 [2M + Na]+: 1107.4753; found: 1107.4759; m/z calcd for C66H60KN12O4 [2M + K]+: 1123.4492; found: 1123.4509. N-(tert-Butyl)-9-methyl-5-(4-methylbenzyl)-4-oxo-3-phenyl-5,6-dihydro-4H-[1,2,3]triazolo[5′,1′:3,4][1,4]diazepino[5,6-b]quinoline-6-carboxamide (6o) Pale yellow solid (0.435 g, 80%); mp 272–274 °C. IR (KBr): νmax = 3340 (NH), 1667 (C=O) cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.85 (s, 9 H, CMe3), 2.34 (s, 3 H, Me), 2.56 (s, 3 H, Me), 4.93 (s, 2 H, CH2Ph), 5.08 (s, 2 H, CH and NH), 7.13 (d, J = 7.8 Hz, 2 H, Ar), 7.26 (d, J = 7.8 Hz, 2 H, Ar), 7.41–7.53 (m, 4 H, Ar), 7.64–7.67 (m, 2 H, Ar), 8.05–8.08 (m, 2 H, Ar), 8.13 (d, J = 8.7 Hz, 1 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.1 (Me), 21.7 (Me), 27.8 (CMe 3), 51.6 (CMe3), 52.2 (CH2Ph), 63.1 (CH), 123.6, 126.1, 126.2, 127.5, 127.7, 128.4, 128.6, 129.1, 129.3, 129.4, 129.9, 132.7, 134.0, 138.6, 138.8, 138.9, 144.2, 145.5, 149.9, 158.9 (C=O), 164.8 (C=O) ppm. HRMS (ESI): m/z calcd for C33H33N6O2 [M + H]+: 545.2664; found: 545.2660; m/z calcd for C33H32N6NaO2 [M + Na]+: 567.2482; found: 567.2479; m/z calcd for C33H32KN6O2 [M + K]+: 583.2223; found: 583.2218; m/z calcd for C66H65KO4 [2M + H]+: 1089.5259; found: 1089.5246; m/z calcd for C66H64N12NaO4 [2M + Na]+: 1111.5072; found: 1111.5066; m/z calcd for C66H64KN12O4 [2M + K]+: 1127.4817; found: 1127.480. Colorless crystal (needle), dimensions 0.150 × 0.040 × 0.021 mm3, crystal system monoclinic, space group P21/c, Z = 4, a = 13.6737(4) Å, b = 16.7252(5) Å, c = 13.3234(4) Å, α = 90°, β = 114.541(2)°, γ = 90°, V = 2771.75(15) Å3, ρ = 1.305 g/cm3, T = 100(2) K, θ max = 68.565°, radiation Mo Kα, λ = 1.54186 Å, 0.5° omega scans with CCD area detector, covering the asymmetric unit in reciprocal space with a mean redundancy of 5.06 and a completeness of 99.0% to a resolution of 0.83 Å, 25512 reflections measured, 5035 unique (R(int) = 0.0374), 3856 observed (I > 2σ(I)), intensities were corrected for Lorentz and polarization effects, an empirical scaling and absorption correction was applied using X-Area LANA 1.70.0.0 (STOE, 2017) based on the Laue symmetry of the reciprocal space, μ = 0.67 mm–1, T min = 0.61, T max = 1.84, structure refined against F 2 with a full-matrix least-squares algorithm using the SHELXL-2016/6 (Sheldrick, 2016) software,23 376 parameters refined, hydrogen atoms were treated using appropriate riding models, goodness of fit 1.03 for observed reflections, final residual values R1(F) = 0.057, wR(F 2) = 0.157 for observed reflections, residual electron density –0.30 to 0.32 eÅ–3. CCDC 1578505 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
    • 23a Krause L. Herbst-Irmer R. Sheldrick GM. Stalke D. J. Appl. Crystallogr. 2015; 48: 3
    • 23b Sheldrick GM. Acta Crystallogr., Sect. C: Struct. Chem. 2015; 71: 3