2-Carbamimidoylbenzoic Acid as a New Effective and Available Precursor for the Synthesis of Substituted 2-(Pyrimidin-2-yl)benzoic Acids

Abstract

A new approach to the synthesis of 2-(pyrimidin-2-yl)benzoic acids based on the ring contraction of the 2-carbamimidoylbenzoic acid [(2-amidinobenzoic) acid] with 1,3-dicarbonyl compounds and their synthetic equivalents has been developed. The intramolecular condensation of the obtained acids with 1,3-dielectrophiles proceeds with the formation of the 4,6-dihydropyrimido[2,1-a]isoindole-4,6-dione system, the pyrrolidone ring of which is easily opened under the action of weak nucleophiles. The reaction of 2-amidinobenzoic acid with chromones, which have an aryloxy group at 3-position does not stop at the step of pyrimidine ring formation and undergoes further spontaneous cyclization into 2-(benzo[4,5]furo[3,2-d]pyrimidin-2-yl)benzoic acids.

Key words

2-carbamimidoylbenzoic acid - ring closure - 2-(pyrimidin-2-yl)benzoic acids - 4,6-dihydropyrimido[2,1-a]isoindole-4,6-dione - chromone ring opening - green chemistry

Publication History

Received: 25 June 2020

Accepted after revision: 16 September 2020

Article published online:
16 November 2020

• References

• 1 Jain KS, Arya N, Inamdar NN, Auti PB, Unawane SA, Puranik HH, Sanap MS, Inamke AD, Mahale VJ, Prajapati CS, Shishoo CJ. Curr. Top. Med. Chem. 2016; 16: 3133
• 2 Large JM, Torr JE, Raynaud FI, Clarke PA, Hayes A, di Stefano F, Urban F, Shuttleworth SJ, Saghir N, Sheldrake P, Workman P, McDonald E. Bioorg. Med. Chem. Lett. 2011; 19: 836
• 3 Xu Z, Liu Z, Chen T, Chen T, Wang Z, Tian G, Shi J, Wang X, Lu Y, Yan X, Wang G, Jiang H, Chen K, Wang S, Xu Y, Shen J, Zhu W. J. Med. Chem. 2011; 54: 5607
• 4 Negoro K, Yonetoku Y, Maruyama T, Yoshida S, Takeuchi M, Ohta M. Bioorg. Med. Chem. 2012; 20: 2369
• 5 Dahlgren MK, Garcia AB, Hare AA, Tirado-Rives J, Leng L, Bucala R, Jorgensen WL. J. Med. Chem. 2012; 55: 10148
• 6 Uehara F, Shoda A, Aritomo K, Fukunaga K, Watanabe K, Ando R, Shinoda M, Ueno H, Kubodera H, Sunada S, Saito K.-I, Kaji T, Asano S, Eguchi J, Yuki S, Tanaka S, Yoneyama Y, Niwa T. Bioorg. Med. Chem. Lett. 2013; 23: 6928
• 7 Caroff E, Meyer E, Treibe A, Hilpert K, Riederer MA. Bioorg. Med. Chem. Lett. 2014; 24: 4323
• 8 Lan Y, Chen Y, Cao X, Zhang J, Wang J, Xu X, Qiu Y, Zhang T, Liu X, Liu B.-F, Zhang G. J. Med. Chem. 2014; 57: 10404
• 9 Vidal M, García-Arriagada M, Rezende MC, Domínguez M. Synthesis 2016; 48: 4246
• 10 Gurney ME, Nugent RA, Mo X, Sindac JA, Hagen TJ, Fox DIII, O’Donnell JM, Zhang C, Xu Y, Zhang H.-T, Groppi VE, Bailie M, White RE, Romero DL, Vellekoop AS, Walker JR, Surman MD, Zhu L, Campbell RF. J. Med. Chem. 2019; 62: 4884
• 11 Krapf MK, Gallus J, Wiese M. J. Med. Chem. 2017; 60: 4474
• 12 Maurya HK, Gupta A. RSC Adv. 2014; 4: 22106
• 13 Engel J, Richters A, Getlik M, Tomassi S, Keul M, Termathe M, Lategahn J, Becker C, Mayer-Wrangowski S, Grütter C, Uhlenbrock N, Krüll J, Schaumann N, Eppmann S, Kibies P, Hoffgaard F, Heil J, Menninger S, Ortiz-Cuaran S, Heuckmann J, Tinnefeld V, Zahedi RP, Sos ML, Schultz-Fademrecht C, Thomas RK, Kast SM, Rauh D. J. Med. Chem. 2015; 58: 6844
• 14 Li X, Shi B, Teng Y, Cheng Y, Yang H, Li J, Wang L, He S, You Q, Xiang H. Med. Chem. Commun. 2019; 10: 294
• 15 Luo G, Tang Z, Lao K, Li X, You Q, Xiang H. Eur. J. Med. Chem. 2018; 150: 783
• 16 Filipski KJ, Guzman-Perez A, Bian J, Perreault C, Aspnes GE, Didiuk MT, Dow RL, Hank RF, Jones CS, Maguire RJ, Tu M, Zeng D, Liu S, Knafels JD, Litchfield J, Atkinson K, Derksen DR, Bourbonais F, Gajiwala KS, Hickey M, Johnson TO, Humphries PS, Pfefferkorn JA. Bioorg. Med. Chem. Lett. 2013; 23: 4571
• 17 Li Q, Hu G, Hu L, Chen Z. Patent CN110305125 A, 2019 ; Chem. Abstr. 2019, 172, 307040.
• 18 Kim C, Nakai T, Wai-Ho Lee T, Moore J, Perl NR, Rohde J, Iyengar RR, Mermerian A. Patent WO 2012003405 2012 ; Chem. Abstr. 2012, 156, 148433.
• 19 Almstead N, Karp GM, Wilde R, Welch E, Ren H. Patent WO 2006/044505 A2, 2006 ; Chem. Abstr. 2006, 144, 432841
• 20 Shaw AN, Duffy KJ, Tedesco R, Wiggall K. US Patent 2008/0171756 A1, 2008 ; Chem. Abstr. 2008, 149, 176630.
• 21 Alexander RP, Bailey S, Brand S, Brookings DC, Brown JA, Haughan AF, Kinsella N, Lowe C, Mack SR, Pitt WR, Richard MD, Sharpe A, Tait LJ. Patent WO2007/141504 A1, 2007 ; Chem. Abstr. 2007, 148, 54880.
• 22 Juby PF, Partyka RA. US Patent 4031093, 1977 ; Chem. Abstr. 1977, 87, 102377.
• 23a Harris RL. N, Huppatz JL, Teitei T. Aust. J. Chem. 1979; 32: 669
• 23b Reimlinger H, Billiau F, Peiren MA. Merényi R. Chem. Ber. 1972; 105: 108
• 24a Hordiyenko OV, Biitseva AV, Kostina YuYu, Zubatyuk RI, Shishkin OV, Groth UM, Kornilov MYu. Struct. Chem. 2017; 28: 607
• 24b Tkachuk VA, Omelchenko IV, Hordiyenko OV. Synlett 2017; 28: 851
• 25 Gong Y, Pauls HW. Synlett 2000; 829
• 26 Sato M, Ogasawara H, Kato T. J. Heterocycl. Chem. 1983; 20: 87
• 27 Coleman PJ, Schreier JD, Cox CD, Breslin MJ, Whitman DB, Bogusky MJ, McGaughey GB, Bednar RA, Lemaire W, Doran SM, Fox SV, Garson SL, Gotter AL, Harrell CM, Reiss DR, Cabalu TD, Cui D, Prueksaritanont T, Stevens J, Tannenbaum PL, Ball RG, Stellabott J, Young SD, Hartman GD, Winrow CJ, Renger JJ. ChemMedChem 2012; 7: 415
• 28 King FE, King TJ, Muir ІH. M. J. Chem. Soc. 1946; 5
• 29 Maggiolo A, Phillips AP, Hitchings GH. J. Am. Chem. Soc. 1951; 73: 106
• 30 Cheung HT. A, Gray PG. J. Labelled Compd. Radiopharm. 1984; 21: 471
• 31 Dunn AD. J. Heterocycl. Chem. 1984; 21: 965
• 32 Tkachuk V, Merkulova V, Omelchenko I, Arrault A, Hordiyenko O. Tetrahedron Lett. 2019; 60. 1959
• 33 Matulková I, Andreoni R, Císařová I, Němec I, Fábry J. Z. Kristallogr. 2017; 232: 471
• 34 Kenner GW, Lythgoe B, Todd AR, Topham A. J. Chem. Soc. 1943; 388
• 35 Joule JA, Mills K. Heterocyclic Chemistry, 4th ed. Blackwell Science; Oxford: 2000
• 36 Babichev FS, Kovtunenko VA, Ishchenko VV, Tyltin AK, Yudina TA. Chem. Heterocycl. Compd. 1985; 21: 1395
• 37 Gaozza CH, Grinberg H, Lamdan S. J. Heterocycl. Chem. 1972; 9: 883
• 38 Boyd GV. In The Chemistry of Amidines and Imidates, Vol. 2. Patai S, Rappoport Z. Wiley; New York: 1991: 367
• 39 Khilya VP, Kornilov MYu, Gorbulenko NV, Golubushina GM, Kovtun EN, Kolotusha NV, Panasenko GV. Chem. Heterocycl. Compd. 1985; 21: 1273
• 40a Khilya VP, Turov AV, Tkachuk TM, Shevchuk LI. Chem. Nat. Compd. 2001; 37: 307
• 40b Sosnovskikh VYa, Usachev BI, Sizov AYu, Barabanov MA. Synthesis 2004; 942
• 40c Frasinyuk MS, Bondarenko SP, Khilya VP. Chem. Nat. Compd. 2006; 42: 673
• 41 Pivovarenko VG, Tkachuk TM. Ukr. Bioorg. Acta 2005; 2: 22
• 42 Tkachuk Т. М. J. Org. Pharm. Chem. 2008; 6: 81
• 43 Vaidya VP, Agasimundin YS. Indian J. Chem. Sect. B: Org. Chem. Incl. Med. Chem. 1981; 20: 114
• 44 Malik WU, Mahesh VK, Raishighani M. Indian J. Chem. 1971; 9: 655
• 45a Chang M.-Y, Chen Y.-H, Wang H.-S. J. Org. Chem. 2018; 83: 2361
• 45b Chao B, Lin S, Ma Q, Lu D, Hu Y. Org. Lett. 2012; 14: 2398
• 45c Stengel I, Wolleb A, Wolleb H, Heinemeyer U, Nagashima H. Patent WO2015/114102, 2015 ; Chem. Abstr. 2015, 163, 295886.
• 46 CCDC 1993264 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 47 Zefirov YuV. Kristallographiya (Russian) 1997; 42: 936
• 48 Sheldrick GM. Acta Crystallogr., Sect. A 2008; 64: 112