All reagents and chemicals were purchased from commercial sources (Sigma-Aldrich S.A. and Riedel-de Haën, Sofia, Bulgaria) and used as received. Melting points were determined on a Boetius hot stage apparatus and are uncorrected. The NMR spectral data were recorded on a Bruker Avance II+600 spectrometer (BAS-IOCCP—Sofia, Bruker, Billerica, MA, USA). 1H-NMR and 13C-NMR spectra for compound 3 were taken in DMSO-d6 at 600 MHz and at 150.9 MHz, respectively. Chemical shifts are given in relative ppm and were referenced to tetramethylsilane (TMS) (δ = 0.00 ppm) as an internal standard; the coupling constants are indicated in Hz. The NMR spectra were recorded at room temperature (ac. 295 K). Mass analyses were carried out on a Q Exactive Plus mass spectrometer (Thermo Fisher Scientific, Waltham, MA, USA). TLC was carried out on precoated 0.2 mm Fluka silica gel 60 plates (Merck KGaA, Darmstadt, Germany), using diethyl ether/n-hexane = 1/1 as a chromatographic system.
Synthesis of N-(2-(1H-Indol-3-yl)ethyl)-2-(6-chloro-9H-carbazol-2-yl)propanamide 3
N,N’-dicyclohexylcarbodiimide (1 mmol) was added to a solution of carprofen (1mmol) in CH2Cl2. The reaction mixture was stirred at room temperature for 10 min. After the addition of tryptamine (1 mmol), the reaction mixture was stirred for 50 min and the formation of white crystalline dicyclohexylurea was observed and then separated by filtration over a sintered glass filter. The filtrate was washed with a diluted hydrochloric acid, a saturated solution of Na2CO3, and brine. The combined organic layers were dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The compound was purified by filtration through short column chromatography (silica gel 60, 70–230 mesh, Merck; diethyl ether).
N-(2-(1H-indol-3-yl)ethyl)-2-(6-chloro-9H-carbazol-2-yl)propanamide (3): white solid (m.p. 186–189 °C), yield 96%, 1H-NMR (600 MHz, DMSO) δ 11.01 (s, 1H), 10.44 (s, 1H), 8.02 (d, J = 1.9 Hz, 1H), 7.95–7.92 (m, 1H), 7.62 (s, 1H), 7.44–7.37 (m, 3H), 7.25 (dd, J = 13.3, 4.9 Hz, 2H), 7.05 (dd, J = 16.8, 8.2 Hz, 1H), 6.98–6.93 (m, 2H), 6.86 (t, J = 7.4 Hz, 1H), 3.68 (q, J = 7.1 Hz, 1H), 3.31–3.27 (m, 2H), 2.79–2.70 (m, 2H), 1.36 (d, J = 7.0 Hz, 3H). 13C-NMR (151 MHz, DMSO) δ 173.86 (C=O), 141.62 (C, Ar), 141.26 (C, Ar), 138.99 (C, Ar), 136.91 (C, Ar), 127.86 (C, Ar), 125.32 (C, Ar), 124.37 (C, Ar), 123.42 (CH), 122.96 (C, Ar), 121.29 (C, Ar), 120.80 (C, Ar), 120.61 (C, Ar), 119.86 (C, Ar), 119.44 (C, Ar), 118.67 (C, Ar), 118.64 (C, Ar), 112.69 (C), 112.53 (C, Ar), 111.76 (C, Ar), 110.19 (C, Ar), 48.17 (CH), 46.39 (CH2), 33.78 (CH2), 24.85 (CH3). λmax, MeOH: 224 (ε = 35 000), 241 (ε = 30 000), 265 (ε = 15 000), 303 (ε = 13 000) nm. HRMS Electrospray ionization (ESI) m/z calcd for C25H23ClN3O+ = 416.1524, found 416.1526 (mass error Δm = −0.48 ppm). IR(KBr) νmax, cm−1: 506 ν, δ (C=C-Cl), 1106 (p-Cl-C=C Ar), 1233, 1266 δas ((-(C=O)-N(R)-H), 1657 ν (C=O), 3101, 3366 ν(-(C=O)-N(R)-H).