1,2-Dichloroethane → N-[(1S)-1-({(1S,4S)-5-[(5-cyano-2,3'-bipyridin-6'-yl)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 10 ml vial was added N-{(1S)-1-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylcarbonyl]-2,2-dimethylpropyl}-1H-indole-2-carboxamide (100 mg, 0.268 mmol), EDC (128 mg, 0.670 mmol), HOBt (41.0 mg, 0.268 mmol), 5-cyano-2,3′-bipyridine-6′-carboxylic acid (74.7 mg, 0.322 mmol) mmol), CH2Cl2 (2.8 ml), DMF (5.0 ml) and DIEA (0.187 ml, 1.072 mmol). The mixture was stirred at room temperature for 1 h, then at 60° C. for 3 h. After cooling to room temperature, the mixture was diluted with CH2Cl2 and sat. Na2CO3. The organic layer was passed over a phase separator, concentrated and purified by reverse phase HPLC: 30×75 mm sunfire column 50 ml/min, 0.1% TFA, 20-60% ACN/Water over 14 min. The fractions containing the product were combined and diluted with CH2Cl2 and sat. NaHCO3. The organic layer was separated, passed over a phase separator and concentrated to afford the desired product as an off white solid (75 mg, 0.132 mmol) as an off white solid. LCMS (m/z): 562.3 (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), 3.37-4.10 (m, 4H), 4.25-5.26 (m, 3H), 6.82-7.68 (m, 5H), 7.87-7.79 (m, 5H), 8.85-9.52 (m, 2H), 11.44-11.92 (m, 1H).

Provenance & Evidence