Reaction Steps
In a 100 mL round-bottomed flask was dissolved tert-butyl (5S,6S,9R)-6-(2,3-difluorophenyl)-9-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-ylcarbamate (40 mg, 0.102 mmol) (azeotroped with dry benzene) and 1-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (41.5 mg, 0.133 mmol) in dimethylformamide (1 mL) to give a colorless suspension under nitrogen. After cooling to −15° C. (ice/methanol bath), NaI-RN/IDS (0.378 mL, 0.378 mmol) was added dropwise. The cooling bath was removed and the resulting tan solution was stirred under nitrogen at rt for 2 h. LCMS showed complete conversion. The reaction was quenched with sodium bicarbonate solution, and diluted with ethyl acetate. The layers were separated. The organic layer was washed with brine, dried with sodium sulfate, and concentrated to give a slightly tan oil. Purification by flash column chromatography up to 10% methanol (with 2M ammonia)/methylene chloride afforded the desired product (39.5 mg, 61%) as a white solid: 1H NMR (400 MHz, CDCl3) δ 11.17 (s, 1H), 8.53 (s, 1H), 8.49 (s, 1H), 8.12 (d, J=5.0 Hz, 1H), 7.43 (d, J=6.0 Hz, 1H), 7.33-7.26 (m, 1H), 7.05 (dt, J=7.8, 5.9 Hz, 3H), 6.34 (d, J=8.8 Hz, 1H), 6.15 (d, J=11.0 Hz, 1H), 5.36-5.25 (m, 1H), 4.63 (t, J=12.4 Hz, 2H), 4.46 (s, 1H), 3.07 (t, J=9.7 Hz, 3H), 2.62 (dd, J=23.9, 11.8 Hz, 1H), 2.49-2.26 (m, 3H), 2.21 (d, J=12.0 Hz, 1H), 2.03-1.78 (m, 3H), 1.23 (s, 9H).
