1,2-Dichloroethane → N-{(1S)-1-[((1S,4S)-5-{[5-(4-cyanophenyl)-2-pyridinyl]carbonyl}-2,5-diazabicyclo[2.2.1]hept-2-yl)carbonyl]-2,2-dimethylpropyl}-1H-indole-2-carboxamide

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Reaction Steps

To a 200 ml flask was added 5-(4-cyanophenyl)-2-pyridinecarboxylic acid (0.76 g, 3.39 mmol), N-{(1S)-1-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylcarbonyl]-2,2-dimethylpropyl}-1H-indole-2-carboxamide (1 g, 2.82 mmol), EDC (1.30 g, 6.77 mmol), HOBt (0.52 g, 3.39 mmol), CH2Cl2 (28 ml), DIEA (1.971 ml, 11.29 mmol). The mixture was stirred at room temperature overnight then diluted with CH2Cl2, water and sat. Na2CO3. The two layers were separated and the organic washed with 2N HCl, sat. NaHCO3 and brine. The CH2Cl2 was passed over a phase separator and concentrated to afford a brown residue. The residue was purified by reverse phase chromatography on a Biotage SP4 with a 65i column at a flow rate of 65 ml/min, 0.1% TFA eluting with 2CV water, the 0-100% ACN/Water over 20 CV. The fractions containing the product were combined and diluted with CH2Cl2 and sat. NaHCO3. The layers were separated and the CH2Cl2 was dried and concentrated to afford the desired product (1.0 g, 1.75 mmol) as an off white solid. LCMS (m/z): 561.3 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.99 (s, 1H), 1.02-1.07 (m, 4H), 1.10 (s, 4H), 1.74-2.12 (m, 2H), 3.37-4.03 (m, 4H), 4.55-5.26 (m, 3H), 6.87-7.24 (m, 2H), 7.26-7.68 (m, 3H), 7.78-8.41 (m, 7H), 8.48-9.18 (m, 1H), 11.52-11.87 (m, 1H).

Provenance & Evidence