Hantzsch-Like One-Pot Three-Component Synthesis of Heptaazadicyclopenta[a,j]anthracenes: A New Ring System

Abstract

A concise and efficient approach to novel tetrahydroheptaazadicyclopenta[a,j]anthracene-5,7-diones, by the reaction of aldehydes with two moles of 7-amino-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-one is reported. Also, pyrazolo[1,5-a]pyrido[3,2-e]pyrimidine-7-carbonitrile derivatives were prepared by a three-component reaction of aldehydes, 7-amino-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-one, and 3-aminocrotononitrile.

Key words

pyrazolopyrimidinones - Hantzsch reaction - heptaazadicyclopentaanthracenes - pyrazolopyridopyrimidines - multicomponent reaction

• References and Notes

• 1 Candeias NR, Montalbano F, Cal PM. S. D, Gois PM. P. Chem. Rev. 2010; 110: 6169
• 2 Isambert N, del Mar Sanchez Duque M, Plaquevent J.-C, Génisson Y, Rodriguez J, Constantieux T. Chem. Soc. Rev. 2011; 40: 1347
• 3 Shiri M. Chem. Rev. 2012; 112: 3508
• 4 Dömling A, Wang W, Wang K. Chem. Rev. 2012; 112: 3083
• 5 Brauch S, van Berkel SS, Westermann B. Chem. Soc. Rev. 2013; 42: 4948
• 6 Safak C, Simsek R. Mini-Rev. Med. Chem. 2006; 6: 747
• 7 Wollmann J, Baumert C, Erlenkamp G, Sippl W, Hilgeroth A. ChemBioChem 2008; 9: 874
• 8 Tusell JM, Barrón S, Serratosa J. Brain Res. 1993; 622: 99
• 9 Wachter GA, Davis MC, Martin AR, Franzblau SG. J. Med. Chem. 1998; 41: 2436
• 10 Murthy YL. N, Rajack A, Taraka Ramji M, Jeson babu J, Praveen C, Aruna Lakshmi K. Bioorg. Med. Chem. Lett. 2012; 22: 6016
• 11 Samzadeh-Kermani A, Shafaroodi H, Miri R, Mirkhani H, Vosooghi M, Shafiee A. Med. Chem. Res. 2009; 18: 112
• 12 Choi S.-J, Cho J.-H, Im I, Lee S.-D, Jang J.-Y, Oh Y.-M, Jung Y.-K, Jeon E.-S, Kim Y.-C. Eur. J. Med. Chem. 2010; 45: 2578
• 13 Fraley ME, Hoffman WF, Rubino RS, Hungate RW, Tebben AJ, Rutledge RZ, McFall RC, Huckle WR, Kendall RL, Coll KE, Thomas KA. Bioorg. Med. Chem. Lett. 2002; 12: 2767
• 14 Wustrow DJ, Capiris T, Rubin R, Knobelsdorf JA, Akunne H, Davis MD, MacKenzie R, Pugsley TA, Zoski KT, Heffner TG, Wise LD. Bioorg. Med. Chem. Lett. 1998; 8: 2067
• 15 Gopalsamy A, Yang H, Ellingboe JW, Tsou H.-R, Zhang N, Honores E, Powell D, Miranda M, McGinnis JP, Rabindran SK. Bioorg. Med. Chem. Lett. 2005; 15: 1591
• 16 Senga K, Novinson T, Wilson HR, Robins RK. J. Med. Chem. 1981; 24: 610
• 17 Sanad SM. H, Kassab RM, Abdelhamid IA, Elwahy AH. M. Heterocycles 2016; 92: 910
• 18 Sroor FM, Abdelmoniem AM, Abdelhamid IA. ChemistrySelect 2019; 4: 10113
• 19 Fares IM. Z, Mekky AE. M, Elwahy AH. M, Abdelhamid IA. Synth. Commun. 2020; in press DOI: 10.1080/00397911.2020.1725575
• 20 Abdella AM, Abdelmoniem AM, Butenschön H, Abdelhamid IA, Elwahy AH. M. ARKIVOC 2019; (vi): 306
• 21 Abdella AM, Moatasim Y, Ali MA, Elwahy AH. M, Abdelhamid IA. J. Heterocycl. Chem. 2017; 54: 1854
• 22 Mohamed MF, Darweesh AF, Elwahy AH. M, Abdelhamid IA. RSC Adv. 2016; 6: 40900
• 23 Abdella AM, Mohamed MF, Mohamed AF, Elwahy AH. M, Abdelhamid IA. J. Heterocycl. Chem. 2018; 55: 498
• 24 Abdelmoniem AM, Ghozlan SA. S, Abdelmoniem DM, Elwahy AH. M, Abdelhamid IA. J. Heterocycl. Chem. 2017; 54: 2844
• 25 Ghozlan SA. S, Ramadan MA, Abdelmoniem AM, Abdelhamid IA. ARKIVOC 2019; (v): 30
• 26 CCDC 1901467 contains the supplementary crystallographic data for compound 5. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 27 Heptaazadicyclopenta[a,j]anthracene-5,7-diones 7a–e; General Procedure A mixture of 7-amino-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5(4H)-one (5; 0.54 g, 2.25 mmol) and the appropriate aromatic aldehyde 6 (1 mmol) was refluxed in glacial HOAc (15 mL) for 12 h. The solvent was evaporated under reduced pressure and the residue was treated with 2 N aq NaHCO₃ (25 mL). The collected crude products were purified by crystallization from EtOH–1,4-dioxane (2:1; 15 mL). 6-(4-Chlorophenyl)-2,10-dimethyl-3,9-diphenyl-4,6,8,11a,12,12b-hexahydro-1,4,8,11,11a,12,12b-heptaazadicyclopenta[a,j]anthracene-5,7-dione (7c) Yellow powder; yield: 0.48 g (79%); mp 240–242 °C. IR (KBr): 3394 (2NH), 3316 (br, 2NH₂) 1651 (2CO) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.30 (s, 6 H, 2CH ₃), 5.83 (s, 1 H, CH), 7.17–7.42 (m, 14 H, ArH), 11.87 (br s, 3 H, 3NH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.7, 34.9, 88.6, 101.9, 126.5, 128.6, 128.8, 129.3, 129.4, 131.7, 132.9, 141.8, 145.3, 149.7, 161.1, 167.5. MS (EI, 70 eV): m/z 586 [M]⁺. Anal. Calcd for C₃₃H₂₄ClN₇O₂: C, 67.63; H, 4.13; N, 16.73. Found: C, 67.82; H, 4.34; N, 16.92.
• 28 Pyrazolo[1,5-a]pyrido[3,2-e]pyrimidine-7-carbonitriles 14a–c; General Procedure A mixture of 7-amino-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5(4H)-one (5; 0.24 g, 1 mmol), the appropriate aromatic aldehyde 6 (1 mmol), and 3-aminocrotononitrile (13; 0.08 g, 1 mmol) in anhyd pyridine (10 mL) was refluxed for 5 h. The solvent was evaporated under reduced pressure and the residue was treated with 0.2 N aq HCl (25 mL). The collected crude products were purified by crystallization from 2:1 EtOH­–1,4-dioxane (15 mL). 2,8-Dimethyl-5-oxo-3,6-diphenyl-4,5,6,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine-7-carbonitrile (14a) Yellow powder; yield: 0.32 g (82%); mp >300 °C. IR (KBr): 3402 (br, 2NH), 2206 (CN), 1622 (CO) cm^–1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.25 (s, 3 H, CH ₃), 2.34 (s, 3 H, CH ₃), 4.61 (s, 1 H, CH), 7.21–7.41 (m, 10 H, ArH), 10.50 (br s, 1 H, NH), 11.60 (br s, 1 H, NH). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 12.8, 17.9, 40.3, 86.5, 89.0, 107.2, 120.9, 126.4, 126.8, 127.6, 128.3, 128.4, 129.1, 129.3, 130.2, 138.9, 144.7, 146.6, 155.2, 159.3. MS (EI, 70 eV): m/z 393 [M]⁺. Anal. Calcd for C₂₄H₁₉N₅O: C, 73.27; H, 4.87; N, 17.80. Found: C, 73.47; H, 4.69; N, 17.68.