Example 48
TEA (2.07 mL, 14.8 mmol) was added to a stirred suspension of 6-(3,3-dimethylpyrrolidin-1-yl)quinoline-4-carboxylic acid Intermediate 106 (347 mg, 0.74 mmol), (R)-3-glycylthiazolidine-4-carbonitrile hydrochloride Intermediate 4 (385 mg, 1.86 mmol), HOBt (568 mg, 3.71 mmol) and EDC (711 mg, 3.71 mmol) in MeCN (7 mL) and EtOAc (7 mL) at 7° C. The resulting suspension was stirred at 7° C. overnight. The solvent was removed under reduced pressure. The residue was suspended in EtOAc and washed with a solution of sat NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (4×50 mL). The organic layers were combined and washed with water (4×20 mL) and concentrated under reduced pressure. The crude product was purified by preparative HPLC, PrepMethod P, to give the title compound (174 mg, 55%) as an orange solid; HRMS (ESI) m/z [M+H]+ calcd for C22H26N5O2S: 424.1802 found: 424.1806; 1H NMR (300 MHz, DMSO-d6) δ 8.91 (t, 1H), 8.53 (d, 1H), 7.84 (d, 1H), 7.34 (d, 1H), 7.29-7.15 (m, 2H), 5.30 (dd, 1H), 4.89 (d, 1H), 4.71 (d, 1H), 4.27 (d, 2H), 3.51-3.33 (m, overlapping with solvent), 3.15 (s, 2H), 1.80 (t, 2H), 1.14 (s, 3H), 1.13 (s, H).
