Compound 11

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a solution of 7-(3-((4-bromo-3-formylphenoxy)methyl)-1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylic acid 27 (18 mg, 0.03 mmol), bis(pinacolato)diboron (12.6 mg, 0.05 mmol) and potassium acetate KOAc (12 mg, 0.12 mmol) in 1,4-dioxane (0.260 mL) was added PdCl₂(dppf)CH₂Cl₂ adduct (2.2 mg, 2.69 µmol). The resulting solution was stirred for 30 min at 110 °C. The reaction was then cooled to room temperature, diluted with ethyl acetate, filtered and washed with water several times. The organic layer was taken, dried over MgSO₄, filtered, and evaporated. The residue was dissolved in acetonitrile (1 mL) and 1 M HCl (aq, 0.5 mL) added, followed by polymer-supported boronic acid. The reaction was stirred at room temperature overnight, filtered, and evaporated. The crude product was purified by reverse-phase chromatography using 50 to 70% acetonitrile in H₂O with 0.1% TFA, affording pure product 11 as a white powder (6 mg, 33% yield). Spectral data: ¹H NMR (300 MHz, CDCl₃) δ ppm 2.15 (s, 3H), 2.30 (tt, J = 7.40, 6.47 Hz, 2H), 3.40 (t, J = 7.40 Hz, 2H), 3.40 (s, 3H), 3.94 (s, 3H), 4.22 (t, J = 6.47 Hz, 2H), 5.1 (s, 2H), 6.73 (d, J = 6.0 Hz, 1H), 6.95 (dd, J = 9.0, 3.0 Hz, 1H), 7.04-7.15 (m, 3H) 7.32-7.39 (dd, J = 8.0, 7.6 Hz, 1H), 7.38 - 7.43 (m, 2H), 7.46-7.52 (m, 2H), 7.70-7.82 (m, 3H), 8.34-8.41 (m, 1H), 9.47 (s, 1H), 10.55 (s, 1H); ¹³C NMR (600 MHz, CDCl₃): δ ppm 10.13, 22.07, 30.72, 34.04, 36.54, 62.42, 67.57, 104.63, 111.54, 116.63, 118.57, 119.98, 120.03, 120.38, 120.86, 120.95, 122.11, 125.12, 125.15, 125.50, 125.78, 125.96, 126.32, 127.45, 128.06, 130.23, 130.42, 134.52, 137.64, 138.53, 140.29, 141.04, 143.27, 154.77, 160.80, 164.29; MS-ESI (m/z): [M + H]⁺ calcd for C₃₆H₃₄BN₃O₇, 632.27; found 632.2.

PubChemID:

316894722

MDL Molfile:

41589_2016_BFnchembio2174_MOESM21_ESM.mol

ChemDraw:

41589_2016_BFnchembio2174_MOESM22_ESM.cdx