Synlett 2019; 30(05): 567-572
DOI: 10.1055/s-0037-1612106
letter
© Georg Thieme Verlag Stuttgart · New York

A General Synthesis of 7-Phenyl-7,13-dihydro-8H-benzo[6,7]azepino[3,2-c]quinolin-8-ones

Jeremy C. Dobrowolski
a   School of Chemistry, The University of New South Wales, Australia, NSW 2052, Australia
,
Duyen H.T. Nguyen
a   School of Chemistry, The University of New South Wales, Australia, NSW 2052, Australia
,
Benjamin H. Fraser
b   The Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW 2232, Australia
,
Mohan Bhadbhade
c   Solid State & Elemental Analysis Unit, Mark Wainwright Analytical Centre, Division of Research, UNSW Sydney, NSW 2052, Australia
,
David StC. Black
a   School of Chemistry, The University of New South Wales, Australia, NSW 2052, Australia
,
Naresh Kumar*
a   School of Chemistry, The University of New South Wales, Australia, NSW 2052, Australia
› Author Affiliations
We thank the Australian Research Council (ARC) Grant DP180100845 for their financial support. JCD thanks University of New South Wales for an Australian Postgraduate Award (APA) and ANSTO for a Residential Student Scholarship (RSS).
Further Information

Publication History

Received: 09 December 2018

Accepted after revision: 09 January 2019

Publication Date:
13 February 2019 (online)


Abstract

Complex benzazepinoquinolone scaffolds can be accessed from the reaction of 2-aminoacetophenones and oxindole derivatives and feature the seven-membered azepine ring moiety commonly found in a range of drug molecules. The described reaction is generally applicable and allows for rapid access to a diverse range of new structures with further potential to build more elaborate molecules.

Supporting Information

 
  • References and Notes

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  • 17 Representative Procedure for the Preparation of 6i 1-(2-Aminophenyl)-3-(4-bromophenyl)prop-2-en-1-one (0.5 mmol, 0.151 g) and 6-bromooxindole (0.5 mmol, 0.106 g) were dissolved in DMSO (1 mL) at room temperature. Sodium hydroxide (0.5 mmol, 0.020 g) was added, and the reaction mixture was stirred at room temperature in an open vessel for 7 h. After completion of the reaction, water (100 mL) was added and the crude mixture acidified to pH 4–6, followed by extraction with DCM (3 × 50 mL), washing combined organic fractions with brine, and drying over sodium sulfate. The crude product was purified by column chromatography (hexane/ethyl acetate) and concentrated in vacuo to yield an analytically pure pale yellow solid 6i. The product was also crystallised from ethanol to give a single crystal suitable for X-ray crystallographic analysis (0.087 g, 35%); mp 216 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 7.93 (d, J = 8.8 Hz, 1 H), 7.84 (dd, J = 8.3, 1.5 Hz, 1 H), 7.54–7.48 (m, 2 H), 7.44–7.28 (m, 4 H), 7.23 (d4dd, J = 8.4, 6.9, 1.5 Hz, 1 H), 7.10 (s, 2 H), 6.97 (d, J = 2.0 Hz, 1 H), 6.73 (dd, J = 8.4, 1.2 Hz, 1 H), 6.64 (dd, J = 8.7, 2.0 Hz, 1 H), 6.52 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 5.28 (dd, J = 10.8, 3.3 Hz, 1 H), 4.06–3.97 (m, 1 H), 3.20 (dd, J = 17.8, 3.2 Hz, 1 H). 13C NMR (101 MHz, DMSO): δ = 199.79, 199.23, 152.84, 151.03, 139.05, 134.23, 133.56, 131.69, 131.28, 130.28, 127.87, 120.16, 118.85, 117.11, 116.90, 116.02, 114.80, 114.41, 46.79, 43.41, 40.15, 39.94, 39.73, 39.52, 39.31, 39.10, 38.89. IR (ATR): νmax = 3608, 3475, 3349, 2360, 2356, 2035, 1606, 1549 cm–1. HRMS (ESI+, 47 V): m/z calcd for C22H18Br2N2O2 [M + H]: 500.9808; found: 500.9807.
  • 18 Representative Procedure for the Preparation of 7b 1,4-Bis(2-aminophenyl)-2-(4-bromophenyl)butane-1,4-dione (0.57 mmol, 0.240 g) was dissolved in T3P®in 50% DMF (1.14 mmol, 0.363 g), and the reaction mixture was stirred at 80 °C for 24 h. Water (200 mL) was added, and the mixture was extracted with CH2Cl2 (3 × 60 mL). The combined organic extracts were washed with brine, dried over Na2SO4 filtered, and the solvent removed under reduced pressure. The crude product was purified by column chromatography (hexane/ethyl acetate) to give an analytically pure pale solid 7b. The product was also crystallised from ethanol to give a single crystal suitable for X-ray crystallographic analysis (0.132 g, 56%); mp 281 °C. 1H NMR (600 MHz, DMSO-d 6): δ = 9.95 (s, 1 H), 8.88 (s, 1 H), 8.59 (dd, J = 8.7, 1.2 Hz, 1 H), 8.08 (dd, J = 8.4, 1.3 Hz, 1 H), 7.94 (dd, J = 8.0, 1.7 Hz, 1 H), 7.83 (ddd, J = 8.2, 6.8, 1.3 Hz, 1 H), 7.72 (ddd, J = 8.4, 6.9, 1.3 Hz, 1 H), 7.61 (dd, J = 8.4, 1.1 Hz, 1 H), 7.49 (ddd, J = 8.5, 7.0, 1.7 Hz, 1 H), 7.40–7.31 (m, 2 H), 7.03 (ddd, J = 8.0, 6.9, 1.1 Hz, 1 H), 6.74–6.68 (m, 2 H), 5.58 (s, 1 H). 13C NMR (151 MHz, DMSO): δ = 189.01, 152.97, 147.74, 142.79, 142.02, 135.21, 133.63, 131.26, 130.50, 129.83, 129.39, 128.92, 126.50, 123.03, 122.35, 120.27, 120.17, 120.11, 120.03, 114.04, 60.46. IR (ATR): νmax = 3254, 3179, 3078, 3017, 2321, 2115, 1657, 1595, 1522 cm–1. HRMS (ESI+, 47 V): m/z calcd for C23H15BrN2O [M + H]: 415.0441; found: 415.0443.