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-00000083.xml
Download PDF
Synlett 2018; 29(09): 1207-1210
DOI: 10.1055/s-0037-1609338
DOI: 10.1055/s-0037-1609338
letter
One-Pot Highly Regioselective Synthesis of Indole-Fused Pyridazino[4,5-b][1,4]benzoxazepin-4(3H)-ones by a Smiles Rearrangement
We are grateful for financial support from Shandong Province Higher Educational Science and Technology Program (Grant No. J17KA099), Shandong Provincial Natural Science Foundation for Doctors Scholar (Grant No. ZR2017BB016), and the Natural Science Foundation of Linyi University (Grant No. LYDX2016BS092).
Further Information
Publication History
Received: 18 January 2018
Accepted after revision: 13 February 2018
Publication Date:
05 March 2018 (online)
Abstract
A simple and convenient synthesis of indole-fused pyridazino[4,5-b][1,4]benzoxazepin-4(3H)-ones is described. A range of 2-(1H-indol-2-yl)phenols and 4,5-dichloropyridazin-3-ones are compatible with this reaction. A Smiles rearrangement is proposed as a key step in the highly regioselective construction of the products. The easy availability of the starting materials makes this an appealing method in organic synthesis.
Key words
indoles - indolopyridazinobenzoxazepinones - regioselectivity - polycyclic heterocycles - Smiles rearrangementSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1609338.
- Supporting Information
-
References and Notes
- 1 Hallinan EA. Stapelfeld A. Savage MA. Reichman M. Bioorg. Med. Chem. Lett. 1994; 4: 509
- 2 Ouyang X. Tamayo N. Kiselyov AS. Tetrahedron 1999; 55: 2827
- 3 Dols PP. M. A. Folmer BJ. B. Hamersma H. Kuil CW. Lucas H. Ollero L. Rewinkel JB. M. Hermkens PH. H. Bioorg. Med. Chem. Lett. 2008; 18: 1461
- 4 Dorn A. Schattel V. Laufer S. Bioorg. Med. Chem. Lett. 2010; 20: 3074
- 5 Gijsen HJ. M. Berthelot D. Zaja M. Brône B. Geuens I. Mercken M. J. Med. Chem. 2010; 53: 7011
- 6 Binaschi M. Boldetti A. Gianni M. Maggi CA. Gensini M. Bigioni M. Parlani M. Giolitti A. Fratelli M. Valli C. Terao M. Garattini E. ACS Med. Chem. Lett. 2010; 1: 411
- 7 Lu S.-M. Alper H. J. Am. Chem. Soc. 2005; 127: 14776
- 8 Liu Y. Chu C. Huang A. Zhan C. Ma Y. Ma C. ACS Comb. Sci. 2011; 13: 547
- 9 Liu Y. Ma Y. Zhang C. Huang A. Ma C. Synlett 2012; 23: 255
- 10 Sapegin AV. Kalinin SA. Smirnov AV. Dorogov MV. Krasavin M. Synthesis 2012; 44: 2401
- 11 Kochanowska-Karamyan AJ. Hamann MT. Chem. Rev. 2010; 110: 4489
- 12 Li S.-M. Nat. Prod. Rep. 2010; 27: 57
- 13 Cho S.-D. Park Y.-D. Kim J.-J. Lee S.-G. Ma C. Song S.-Y. Joo W.-H. Falck JR. Shiro M. Shin D.-S. Yoon Y.-J. J. Org. Chem. 2003; 68: 7918
- 14 Cho S.-D. Song S.-Y. Park Y.-D. Kim J.-J. Joo W.-H. Shiro M. Falck JR. Shin D.-S. Yoon Y.-J. Tetrahedron Lett. 2003; 44: 8995
- 15 Cho S.-D. Park Y.-D. Kim J.-J. Joo W.-H. Shiro M. Esser L. Falck JR. Ahn C. Shin D.-S. Yoon Y.-J. Tetrahedron 2004; 60: 3763
- 16 Zuo H. Li Z.-B. Ren F.-K. Falck JR. Meng L. Ahn C. Shin D.-S. Tetrahedron 2008; 64: 9669
- 17 Zuo H. Meng L. Ghate M. Hwang K.-H. Cho YK. Chandrasekhar S. Reddy CR. Shin D.-S. Tetrahedron Lett. 2008; 49: 3827
- 18 Zhao Y. Wu Y. Jia J. Zhang D. Ma C. J. Org. Chem. 2012; 77: 8501
- 19 Zhao Y. Dai Q. Chen Z. Zhang Q. Bai Y. Ma C. ACS Comb. Sci. 2013; 15: 130
- 20 Yang B. Tan X. Guo R. Chen S. Zhang Z. Chu X. Xie C. Zhang D. Ma C. J. Org. Chem. 2014; 79: 8040
- 21 Niu X. Yang B. Li Y. Fang S. Huang Z. Xie C. Ma C. Org. Biomol. Chem. 2013; 11: 4102
- 22 Kitching MO. Hurst TE. Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 2925
- 23 Zhou Y. Zhu J. Li B. Zhang Y. Feng J. Hall A. Shi J. Zhu W. Org. Lett. 2016; 18: 380
- 24 Zhan C. Jia J. Yang B. Huang A. Liu Y. Ma C. RSC Adv. 2012; 2: 7506
- 25 Sang P. Yu M. Tu H. Zou J. Zhang Y. Chem. Commun. 2013; 49: 701
- 26 CCDC 1581528 contains the supplementary crystallographic data for compound 3n. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
- 27 Indolo[1,2-d]pyridazino[4,5-b][1,4]benzoxazepin-9(8H)-ones 3a–r; General Procedure The appropriate 2-(1H-indol-2-yl)phenol 1 (0.30 mmol), 2-tetrahydropyranylpyridazin-3-one 2 (0.30 mmol), and K2CO3 (2.5 equiv.) were successively added to a 10 mL Schlenk tube. DMF (2 mL) was then added from a dropper and the resulting solution was stirred at 80 °C for 3 h. The mixture was cooled to r.t. then extracted with EtOAc (×3). The combined organic phase was washed with brine, dried (Na2SO4), and filtered. The solvent was then removed in vacuoto give a crude mixture that was purified by column chromatography (silica gel). 8-(Tetrahydro-2H-pyran-2-yl)indolo[1,2-d]pyridazino[4,5-b][1,4]benzoxazepin-9(8H)-one (3a) Light-yellow solid; yield: 104 mg (90%); mp 122–124 °C. 1H NMR (500 MHz, CDCl3): δ = 8.43 (s, 1 H), 7.72–7.70 (m, 2 H), 7.66 (d, J = 8.2 Hz, 1 H), 7.54–7.52 (m, 1 H), 7.40–7.27 (m, 4 H), 6.98 (s, 1 H), 6.15–6.13 (m, 1 H), 4.17–4.14 (m, 1 H), 3.81–3.76 (m, 1 H), 2.23–2.15 (m, 1 H), 2.07–2.04 (m, 1 H), 1.80–1.71 (m, 3 H), 1.60–1.58 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 157.55, 157.02, 144.65, 136.58, 135.94, 133.09, 131.39, 130.48, 129.45, 129.39, 126.36, 123.99, 123.54, 122.82, 122.15, 121.69, 111.56, 105.97, 83.32, 68.98, 28.99, 24.89, 22.83. HRMS (ESI): m/z [M + H]+ calcd for C23H20N3O3: 386.1499; found: 386.1491.