Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00032269.xml
![](/products/assets/desktop/img/oa-logo.png)
CC BY-ND-NC 4.0 · SynOpen 2017; 01(01): 0008-0010
DOI: 10.1055/s-0036-1588167
DOI: 10.1055/s-0036-1588167
letter
Ultrasound-Accelerated Amide Coupling Reactions Directed toward the Synthesis of 1-Acetyl-3-carboxamide-β-carboline Derivatives of Biological Importance
Further Information
Publication History
Received: 03 February 2017
Accepted after revision: 12 March 2017
Publication Date:
22 March 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00032269/201701/lookinside/thumbnails/so-2017-d0002-l_10-1055_s-0036-1588167-1.jpg)
Abstract
Several biologically important 1-acetyl-3-carboxamide-β-carboline derivatives were rapidly synthesized by ultrasound-promoted amide coupling of 1-acetyl-9H-pyrido[3,4-b]indole-3-carboxylic acid with substituted aromatic amines. The major advantages of the proposed method are that use of ultrasound irradiations afforded the desired products in a drastically reduced reaction time and in excellent yields compared with conventional stirring.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588167.
- Supporting Information
-
References and Notes
- 1a Copp BR. Keyzers RA. Munro MH. G. Princep MR. Nat. Prod. Rep. 2014; 31: 16
- 1b Xiong ZQ. Wang JF. Hao YY. Wang Y. Mar. Drugs 2013; 11: 700
- 2a Cragg GM. Newman DJ. Biochim. Biophys. Acta 2013; 1830: 3670
- 2b Lam KS. Curr. Opin. Microbiol. 2006; 9: 245
- 3 Bailey PD. Cochrane PJ. Forster AH. Morgana KM. Pearson DP. J. Tetrahedron Lett. 1999; 40: 4597
- 4a Zheng C. Fang Y. Tong W. Li G. Zhou HW. Lin Q. Yang F. Yang Z. Wang P. Peng Y. Pang X. Yi Z. Luo J. Liu M. Chen Y. J. Med. Chem. 2014; 57: 600
- 4b Winkler JD. Londregan AT. Hamann MT. Org. Lett. 2006; 8: 2591
- 5 Tang JG. Wang YH. Wang RR. Dong ZJ. Yang LM. Zheng YT. Liu JK. Chemistry & Biodiversity 2008; 5: 447
- 6 Kawasaki T. Higuchi K. Nat. Prod. Rep. 2005; 22: 761
- 7a Herraiz T. Galisteo J. J. Agric. Food Chem. 2003; 51: 7156
- 7b Chen H. Gao P. Zhang M. Liao W. Zhang J. New J. Chem. 2014; 38: 4155
- 8 Ang KK. H. Holmes MJ. Higa T. Hamann MT. Kara UK. Antimicrob. Agents Chemother. 2000; 44: 1645
- 9a Kusurkar RS. Goswami SK. Vyas SM. Tetrahedron Lett. 2003; 44: 4761
- 9b Laine AE. Lood C. Koskinen AM. P. Molecules 2014; 19: 1544
- 10 Airaksinen MM. Kari I. Med. Biol. 1981; 59: 21
- 11 Carbrera GM. Seldes AM. J. Nat. Prod. 1999; 62: 759
- 12 Lippke KP. Schunack WG. Wenning W. Mueller WE. J. Med. Chem. 1983; 26: 499
- 13 Cain M. Weber RW. Guzman F. Cook JM. Barker SA. Rice KC. Crawley JN. Paul SM. Skolnick PJ. Med. Chem. 1982; 25: 1081
- 14 Hagen TJ. Skolnick P. Cook JM. J. Med. Chem. 1987; 30: 750
- 15 Dodd RH. Ouannes C. Carvalho LP. Valin A. Venault P. Chapouthier G. Rossier J. Potier P. J. Med. Chem. 1985; 28: 824
- 16 Patel K. Gadewar M. Tripathi R. Prasad SK. Patel DK. Asian Pac. J. Trop. Biomed. 2012; 2: 660
- 17 Cao R. Peng W. Wang Z. Zu A. Curr. Med. Chem. 2007; 14: 479
- 18 Tang JG. Wang YH. Wang RR. Dong ZJ. Yang LM. Zheng YT. Liu JK. Chemistry & Biodiversity 2008; 5: 447
- 19 Bemis DL. Capedice JL. Gorroochurn P. Katz AZ. Buttyan R. Int. J. Oncol. 2006; 29: 1065
- 20 Cao R. Peng W. Chen H. Ma Y. Liu X. Hou X. Guan H. Xu A. Biochem. Biophys. Res. Commun. 2005; 338: 1557
- 21 Dorey G. Dubois L. Potier P. Dodd RH. J. Med. Chem. 1995; 38: 189
- 22 Winkler JD. Londregan AT. Hamann MT. Org. Lett. 2006; 8: 2591
- 23 Castro AC. Dang LC. Soucy F. Grenier L. Mazdiyansi H. Hottelet M. Parent L. Pien C. Palombella VAdams J. Bioorg. Med. Chem. Lett. 2003; 13: 2419
- 24 Nicolaou KC. Vourloumis D. Winssinger N. Baran PS. Angew. Chem. Int. Ed. 2000; 39: 44
- 25 Ji C. Chen Q. Li Q. Huang H. Song Y. Maa J. Ju J. Tetrahedron Lett. 2014; 55: 4901
- 26 Johannes T. Simurdiak MR. Zhao H. Encyclopedia of Chemical Processing . DOI: 10.1081/E-ECHP-120017565.
- 27 Liu YQ. Li LH. Yang L. Li HY. Chem. Pap. 2010; 64: 533
- 28 Meciarova M. Polackova V. Toma S. Chem. Pap. 2002; 56: 208
- 29 Meciarova M. Toma S. Babiak P. Chem. Pap. 2004; 58: 104
- 30 Tabatabaeian K. Mamaghani M. Mahmoodi NO. Khorshidi A. Catal. Commun. 2008; 9: 416
- 31a Kumar V. Sharma A. Sharma M. Sharma UK. Sinha AK. Tetrahedron 2007; 63: 9718
- 31b Sinha AK. Sharma A. Joshi BP. Tetrahedron 2007; 63: 960
- 32a Sharma N. Chundawat TS. Bhagat S. Synthesis 2016; 48: 4495
- 32b Chundawat TS. Sharma N. Kumari P. Bhagat S. Synlett 2016; 27: 404
- 32c Chundawat TS. Sharma N. Kumari P. Bhagat S. Med. Chem. Res. 2016; 25: 2335
- 33 Conventional method for the synthesis of 9H-pyrido[3,4-b]indole-3-carboxamide derivatives (3a–k); General procedure: To a stirred solution of 1 (1 equiv) in DMF were added EDC·HCl (1.1 equiv) and HOBt (1.1 equiv), followed by addition of DIPEA (2.1 equiv). The resulting reaction mixture was stirred at r.t. for 30 minutes. The requisite amine 2a–c was added portionwise and the reaction was stirred at r.t. for 15–18 h (Table 1). Progress of reaction was monitored by TLC. After completion, the reaction mixture was poured into ice-cold water, and the precipitate filtered. Column chromatography on silica (100–200 mesh), eluting with 30–40% ethyl acetate/hexane gave the pure 1-acetyl-3-carboxamide-β-carboline derivatives 3a–c.Ultrasound method for the synthesis of 1-acetyl-3-carboxamide-β-carboline derivatives (3a–k); General procedure: To a stirred solution of 1 (1equiv) in DMF were added EDC·HCl (1.1 equiv) and HOBt (1.1 equiv), followed by addition of DIPEA (2.1 equiv). The resulting reaction mixture was stirred at r.t. for 10 minutes. The requisite amine 2a–k was added portionwise and the reaction was stirred at r.t. under sonication for the time detailed in Table 1 and Table 2. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into ice-cold water, and the precipitate filtered. Column chromatography on silica (100–200 mesh), eluting with 30–40% ethyl acetate/hexane gave the pure 1-acetyl-3-carboxamide-β-carboline derivatives 3a–k.Representative Spectroscopic Data1-Acetyl-N-phenethyl-9H-pyrido[3,4-b]indole-3-carboxamide (3a): Pale-yellow solid; mp 172–174 °C; IR (KBr): 3349, 2914, 1683, 1534 cm–1; 1H NMR (400 MHz, CDCl3): δ = 10.31 (s, 1 H, -NH), 9.00 (s, 1 H), 8.12 (d, J = 7.63 Hz, 1 H), 8.00 (t, 1 H, -NH), 7.56–7.50 (m, 2 H), 7.31–7.18 (m, 6 H), 3.78 (q, J = 6.78 Hz, 2 H), 2.93 (t, J = 6.78 Hz, 2 H), 2.67 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 202.2, 164.4, 141.4, 139.1, 139.0, 136.1, 133.4, 132.5, 129.6, 128.8, 128.7, 126.5, 122.2, 121.4, 120.9, 118.2, 112.1, 40.4, 35.8, 25.6; HRMS (ESI): m/z [M+H]+ calcd for C22H19N3O2: 358.1555; found: 358.1545.1-Acetyl-N-(2,4-difluorophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (3j): Yellow solid; mp 210–212 °C; IR (KBr): 3350, 2916, 1665, 1539 cm–1; 1H NMR (400 MHz, DMSO-d 6): δ = 12.29 (s, 1 H, -NH), 10.39 (s, 1 H, -NH), 9.19 (s, 1 H), 8.12 (q, J = 6.10 Hz, 1 H), 7.83 (d, J = 7.63 Hz, 1 H), 7.63 (t, J = 8.39 Hz, 1 H), 7.46–7.41 (m, 1 H), 7.34 (t, J = 7.63 Hz, 1 H), 7.17 (t, J = 8.39 Hz, 1 H), 2.93 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 200.6, 162.5, 145.1, 142.9, 142.4, 137.2, 135.0, 133.9, 133.9, 132.2, 129.5, 122.4, 121.0, 120.2, 118.4, 113.4, 111.4, 104.5, 104.2, 25.9; HRMS (ESI): m/z [M+H]+ calcd for C20H13F2N3O2: 366.1054; found: 366.1061
- 34 Huang H. Yao Y. He Z. Yang T. Ma J. Tian X. Li Y. Huang C. Chen X. Li W. Zhang S. Zhang C. Ju J. J. Nat. Prod. 2011; 74: 2122
- 35 Tang J.-G. Liu H. Zhou Z.-Y. Liu J.-K. Synth. Commun. 2010; 40: 1411