Compound 19

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)-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylic acid 18 (34 mg, 0.05 mmol), bis(pinacolato)diboron (25.4 mg, 0.10 mmol) and potassium acetate (24 mg, 0.25 mmol) in 1,4-dioxane (0.521 mL) was added [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (PdCl₂(dppf)CH₂Cl₂, 4.25 mg, 5.20 µmol). The resulting solution was stirred for 30 min at 110 °C. The reaction was diluted with ethyl acetate, washed with H₂O, the organic phase dried over MgSO₄ and concentrated to yield a brown oil. The crude product was purified by reverse-phase chromatography using 50 to 70% acetonitrile in H₂O with 0.1% TFA, affording pure product 19 as white powder (23.8 mg, 34% yield). Spectral data: ¹H NMR (300 MHz, CDCl₃) δ ppm 1.29 (s, 12H), 2.19 (tt, J = 7.40, 6.47 Hz, 2H), 2.24 (s, 3H), 3.38 (t, J = 7.40 Hz, 2H), 3.81 (s, 3H), 4.22 (t, J = 6.47 Hz, 2H), 5.16 (s, 2H), 6.73 (d, J = 6.0 Hz, 1H), 7.07 (dd, J = 9.0, 3.0 Hz, 1H), 7.14 (s, 1H), 7.15 (s, 1H), 7.32-7.39 (dd, J = 8.0, 7.6 Hz, 1H), 7.40 - 7.42 (m, 2H), 7.43-7.48 (m, 2H), 7.49-7.52 (m, 2H), 7.68 (q, J = 3.0 Hz, 1H), 7.79-7.84 (m, 1H), 8.32-8.39 (m, 1H), 9.20 (s, 1H), 10.51 (s, 1H); ¹³C NMR (600 MHz, CDCl₃) δ ppm 10.26, 21.86, 23.93, 25.86, 27.16, 28.39, 32.79, 36.81, 62.42, 66.91, 89.23, 103.92, 104.23, 108.13, 114.30, 119.9, 120.04, 120.77, 121.07, 121.10, 121.67, 121.82, 123.12, 125.09, 125.38, 125.70, 126.57, 127.57, 127.78, 134.17, 134.34, 135.57, 136.28, 139.82, 145.91, 156.00, 156.76, 159.99, 161.42, 193.79; MS-ESI (m/z): [M – H]^- calcd for C₄₁H₄₂BN₃O₇, 698.32; found 698.2.

PubChemID:

316894730

MDL Molfile:

41589_2016_BFnchembio2174_MOESM37_ESM.mol

ChemDraw:

41589_2016_BFnchembio2174_MOESM38_ESM.cdx