Reaction Steps
To a stirred mixture of (6R)-3′-methyl-2′,5′-dioxo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-imidazolidine]-3-carboxylic acid (described in Intermediate 19, 36 mg, 0.139 mmol), (3S,5S,6R)-3-amino-6-methyl-1-(2,2,2-trifluoroethyl)-5-(2,3,5,6-tetrafluorophenyl)piperidin-2-one hydrochloride (described in Intermediate 16, 50 mg, 0.127 mmol), HOBT (25 mg, 0.165 mmol), and EDC (32 mg, 0.165 mmol) in DMF (1.5 mL) was added N,N-diisopropylethylamine (0.066 mL, 0.380 mmol), and the resulting mixture was stirred at ambient temperature for 6 h. The reaction mixture was poured into saturated aqueous sodium bicarbonate (5 mL) and extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:10:1, to give the title compound. HRMS: m/z=602.1632 (M+1), calculated m/z=602.1633 for C26H23F7N5O4. 1H NMR (500 MHz, CDCl3) δ 8.88 (s, 1H), 8.38 (br s, 1H), 8.03 (s, 1H), 7.55 (d, 1H, J=4.9 Hz), 7.08 (m, 4.90 (m, 1H), 4.50 (m, 1H), 4.04-3.95 (m, 2H), 3.70 (d, 1H, J=18.3 Hz), 3.61 (d, 1H, J=17.3 Hz), 3.35 (m, 1H), 3.30 (d, 1H, J=18.1 Hz), 3.20 (d, 1H, J=17.6 Hz), 2.89-2.77 (m, 2H), 2.68 (s, 3H), 1.30 (d, 3H, J=6.4 Hz).
