Easy Access to Novel Tetrahydro-1-benzazepine-2-carboxylic Acids and Tetrahydro-1-benzazepines Carrying [a]-Fused Heterocyclic Units from 2-(Allylaryl)glycinates

Abstract

A concise, efficient, and versatile approach to access novel tetrahydro-1H-benzo[b]azepine-2-carboxylic acids and tricyclic tetra­hydro-1-benzazepines carrying [a]-fused heterocyclic units is reported. The easily accessible 2-(allylaryl)glycinates were used as starting material to synthesize, via the corresponding 1,4-epoxycycloadducts, the required key intermediate benzo[b]azepine-2-carboxylates. Hydrolysis of the latter afforded the targeted benzo[b]azepine-2-carboxylic acids. The key intermediate was also converted into N-2-chloroacetyl derivatives which, in turn, were transformed into the corresponding tricyclic target hexahydrobenzo[f]pyrazino[1,2-a]azepine-1,4-diones by reaction with benzylamine or aminoethanol. The reaction of the common intermediate with hydrazine gave the corresponding intermediate carbohydrazides, which, by reaction with trimethoxymethane, were transformed into another tricyclic target tetrahydrobenzo[f][1,2,4]tri­azino[4,5-a]azepin-4(3H)-ones. Full spectroscopic characterization (IR, HRMS, and ¹H and ¹³C NMR) is also reported for each compound.

Key words

2-(allylaryl)glycinates - intramolecular 1,3-dipolar cyclo­addition - reductive cleavage - cyclocondensation - tricyclic fused-[a]-1-benzazepines

Publication History

Received: 19 July 2020

Accepted after revision: 07 September 2020

Article published online:
15 October 2020

• References

• 1a Schoen WR, Pisano JM, Prendergast K, Wyvratt MJ, Fisher MH, Cheng K, Chan WW.-S, Butler B, Smith RG, Ball RG. J. Med. Chem. 1994; 37: 897
• 1b De Vita RJ, Wyvratt MJ. Drugs Future 1996; 21: 273
• 1c DeVita RJ, Bochis R, Frontier AJ, Kotliar A, Fisher MH, Schoen WR, Wyvratt MJ, Cheng K, Chan WW.-S, Butler B, Jacks TM, Hickey GJ, Schleim KD, Leung K, Chen Z, Chiu S.-HL, Feeney WP, Cunningham PK, Smith RG. J. Med. Chem. 1998; 41: 1716
• 1d Ankersen M. Prog. Med. Chem. 2002; 39: 173
• 1e Morita M, Ohkubo-Suzuki A, Takahashi T, Nagashima A, Sawada Y, Ohkawa T, Nishimura S, Kita Y. Drug Dev. Res. 2003; 60: 241
• 1f Decaux G. Am. J. Med. 2001; 110: 582
• 1g Kakefuda A, Tsukada J, Kusayama T, Tahara A, Tsukamoto S. Bioorg. Med. Chem. Lett. 2002; 12: 229
• 1h Seto M, Miyamoto N, Aikawa K, Aramaki Y, Kanzaki N, Iizawa Y, Baba M, Shiraishi M. Bioorg. Med. Chem. 2005; 13: 363
• 1i Tomasi S, Renault J, Martin B, Duhieu S, Cerec V, Le Roch M, Uriac P, Delcros J. J. Med. Chem. 2010; 53: 7647
• 1j Hirts W, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Priece GW, Medhurst A. Bioorg. Med. Chem. Lett. 2006; 16: 658
• 1k Hoyt SB, London C, Gorin D, Wyvratt MJ, Fisher MH, Abbadie C, Felix JP, Garcia ML, Li X, Lyons K, McGowan E, Macintyre E, Martin W, Priest BT, Ritter A, Smith M, Warren V, Williams B, Kaczorowski GJ, Parsons WH. Bioorg. Med. Chem. Lett. 2007; 17: 4630
• 1l Palm C, Reimann D, Gross P. Cardiovasc. Res. 2001; 51: 403
• 1m Nakamura S, Yamamura Y, Itoh S, Hirano T, Tsujimae K, Aoyama M, Kondo K, Ogawa H, Shinohara T, Kan K, Tanada Y, Teramoto S, Sumida T, Nakayama S, Sekiguchi K, Kambe T, Tsujimoto G, Mori T, Tominaga M. Br. J. Pharmacol. 2000; 129: 1700
• 1n Yea CM, Allan CE, Ashworth DM, Barnett J, Baxter AJ, Broadbridge JD, Franklin RJ, Hampton SL, Hudson P, Horton JA, Jenkins PD, Penson AM, Pitt GR. W, Riviere P, Robson PA, Rooker DP, Semple G, Sheppard A, Haigh RM, Roe MB. J. Med. Chem. 2008; 51: 8124
• 2a Sato T, Ishida S, Ishibashi H, Ikeda M. J. Chem. Soc., Perkin Trans. 1 1991; 353
• 2b Ikeda M, Obata K, Oka J, Ishibashi H, Sato T. Heterocycles 1997; 44: 203
• 2c Fujita K, Yamamoto K, Yamaguchi R. Org. Lett. 2002; 4: 2691
• 2d Dolman SJ, Schrock RR, Hoveyda AH. Org. Lett. 2003; 5: 4899
• 2e Qadir M, Priestley RE, Rising TW. D. F, Gelbrich T, Coles SJ, Hursthouse MB, Sheldrake PW, Whittall N, Hii KK. Tetrahedron Lett. 2003; 44: 3675
• 2f Fujita K, Takahashi Y, Owaki M, Yamamoto K, Yamaguchi R. Org. Lett. 2004; 6: 2785
• 2g Omar-Amrani R, Thomas A, Brenner E, Schneider R, Fort Y. Org. Lett. 2004; 5: 2311
• 2h Ikemoto T, Ito T, Nishiguchi A, Miura S, Tomimatsu K. Org. Process Res. Dev. 2005; 9: 168
• 2i Qadir M, Cobb J, Sheldrake PW, Whittall N, White AJ. P, Hii KK, Horton PN, Hursthouse MB. J. Org. Chem. 2005; 70: 1545
• 3a Giacobbe S, Di Fabio R. Tetrahedron Lett. 2001; 42: 2027
• 3b Mitsunaga S, Ohbayashi T, Sugiyama S, Saitou T, Tadokoro M, Satoh T. Tetrahedron: Asymmetry 2009; 20: 1697
• 4 Prasad C. Peptides 1995; 16: 151
• 5 Park B.-S, Widger W, Kohn H. Bioorg. Med. Chem. 2006; 14: 41
• 6 Sansinenea E, Salazar F, Jiménez J, Mendoza A, Ortiz A. Tetrahedron Lett. 2016; 57: 2604
• 7 Mollica A, Costante R, Fiorito S, Genovese S, Stefanucci A, Mathieu V, Kiss R, Epifano F. Fitoterapia 2014; 98: 91
• 8 Cornacchia C, Cacciatore I, Baldassarre L, Mollica A, Feliciani F, Pinnen F. Mini-Rev. Med. Chem. 2012; 12: 2
• 9 López-Rodríguez ML, Morcillo MJ, Fernández E, Benhamú B, Tejada I, Ayala D, Viso A, Campillo M, Pardo L, Delgado M, Manzanares J, Fuentes JA. J. Med. Chem. 2005; 48: 2548
• 10a Monleón LM, Grande M, Anaya J. Tetrahedron 2007; 63: 3017
• 10b Monleón LM, Díez-García F, Zamora H, Anaya J, Grande M, de Diego JG, Rodríguez FD. Bioorg. Chem. 2012; 45: 29
• 10c Zhao H, Zhang X, Hodgetts K, Thurkauf A, Hammer J, Chandrasekhar J, Kieltyka A, Brodbeck R, Rachwal S, Primus R, Manly C. Bioorg. Med. Chem. Lett. 2003; 13: 701
• 10d Piao F.-Y, Han R.-B, Zhang W, Zhang W.-B, Jiang R.-S. Eur. J. Med. Chem. 2011; 46: 1050
• 10e Zhang WB, Han RB, Zhang W, Jiang RS, Piao FY. Med. Chem. Res. 2012; 21: 2587
• 10f Schmees N, Kuhnke J, Haendler B, Neuhaus R, Lejeune P, Siegel S, Krüger M, Fernandez A, Künzer H, Gallenkamp D. WO 2014/048945 Al, 2014
• 11a Casara P, Le Diguarher T, Geneste O, Hickman J. US 2008/0188400 A1, 2008
• 11b Wang Y, Villa L, Us IL, Akritopoulou-zanze I, Djuric S, Pohlki F, Braje W, Relo A. US 2011/0130382 Al, 2011
• 12a Gómez-Ayala SL, Stashenko E, Palma A, Bahsas A, Amaro-Luis JM. Synlett 2006; 2275
• 12b Acosta LM, Palma A, Bahsas A. Tetrahedron 2010; 66: 8392
• 12c Gómez-Ayala S, Castrillón JA, Palma A, Leal SM, Escobar P, Bahsas A. Bioorg. Med. Chem. 2010; 18: 4721
• 12d Acosta-Quintero LM, Palma A, Nogueras M, Cobo J. Synthesis 2012; 3765
• 12e Blanco MC, Escobar P, Leal SM, Bahsas A, Cobo J, Nogueras M, Palma A. Eur. J. Med. Chem. 2014; 86: 291
• 13 Guerrero SA, Sanabria CM, Palma A, Cobo J, Glidewell C. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2014; 70: 408
• 14 Guerrero SA, Ramírez JE, Palma A, Cobo J, Glidewell C. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2019; 75: 168