Reaction Steps
In a 50 mL round-bottomed flask was dissolved tert-butyl (5S,6S,9R)-6-(2,3-difluorophenyl)-9-(4-(2-oxo-3-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamido)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-ylcarbamate (31 mg, 0.041 mmol) in methylene chloride (1 mL) to give a colorless solution. trifluoroacetic acid (0.5 mL) was added, and the mixture was stirred at rt for 1.5 h: LCMS showed complete conversion. The solvent was removed in vacuo, and the residue was partitioned between ethyl acetate/0.5N sodium hydroxide/saturated sodium bicarbonate solution. The layers were separated. The organic layer was dried and concentrated to give a tan oil. flash column chromatography up to 10% methanol (2M ammonia) in methylene chloride afforded the desired product (12 mg, 55%) as a white solid: MS (ESI) [M+H]+=535.3; 1H NMR (400 MHz, CDCl3) δ 10.98-9.87 (m, 1H), 8.56 (d, J=2.5 Hz, 1H), 8.42 (d, J=2.5 Hz, 1H), 8.07 (dd, J=5.3, 1.2 Hz, 1H), 7.35 (dd, J=7.9, 1.2 Hz, 1H), 7.21-7.05 (m, 4H), 6.98 (dd, J=7.9, 5.3 Hz, 1H), 5.29 (dd, J=10.4, 5.1 Hz, 1H), 4.71-4.55 (m, 2H), 4.35 (d, J=13.6 Hz, 2H), 3.05 (1, J=13.0 Hz, 2H), 2.94 (t, J=9.3 Hz, 1H), 2.53 (t, J=11.7 Hz, 2H), 2.41-2.23 (m, 2H), 2.16-1.69 (m, 6H); 19F NMR (376 MHz, CDCl3) δ −137.32 (ddd, J=21.4, 9.6, 4.5 Hz), −142.66 (d, J=19.5 Hz).
