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Synlett 2018; 29(09): 1207-1210
DOI: 10.1055/s-0037-1609338
letter
© Georg Thieme Verlag Stuttgart · New York

One-Pot Highly Regioselective Synthesis of Indole-Fused Pyridazino[4,5-b][1,4]benzoxazepin-4(3H)-ones by a Smiles Rearrangement

Xiaolei Jiang
School of Chemistry and Chemical Engineering, Linyi University, Linyi, Shandong 276005, P. R. of China   Email: hufangdong@lyu.edu.cn
,
Fangdong Hu*
School of Chemistry and Chemical Engineering, Linyi University, Linyi, Shandong 276005, P. R. of China   Email: hufangdong@lyu.edu.cn
› Author AffiliationsWe 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)

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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 rearrangement

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1609338.
  • Supporting Information
 

  • References and Notes

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  • 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.