Reaction Steps
To (1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (102 mg, 0.20 mmol), N-(3-aminopropyl)-2-pyrrolidinone (85 μL, 0.60 mmol), EDC (58 mg, 0.30 mmol), and HOBt (46 mg, 0.30 mmol) was added N,N-dimethylformamide (2 mL) and triethylamine (140 μL, 1.01 mmol). The mixture was stirred at room temperature for 16 h, quenched with 1:1 water:brine, and extracted with EtOAc. The organic layer was washed with 1:1 water:brine (3×). The organic layer was dried over magnesium sulfate, filtered and purified by reverse phase HPLC (C-18, eluting with a 45:55 to 80:20 gradient of acetonitrile:water+0.1% TFA). The combined fractions were diluted with ethyl acetate and dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated to afford the title compound (97 mg, 0.15 mmol, 76% yield) as a white solid. MS ESI: [M+H]+ m/z 631.2. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.83 (d, J=4.9, 1H), 7.93 (s, 1H), 7.92 (s, 1H), 7.68 (t, J=5.6, 1H), 7.46 (s, 1H), 7.28 (d, J=4.9, 1H), 7.14 (s, 1H), 5.86 (s, 1H), 3.29 (s, 1H), 3.24-3.12 (m, 2H), 3.12-3.03 (m, 1H), 2.99-2.88 (m, 1H), 2.31 (s, 3H), 2.19 (m, 2H), 2.02 (m, 2H), 1.86 (m, 5H), 1.66-1.50 (m, 3H), 1.40 (m, 1H), 1.11 (s, 3H), 0.92 (s, 3H).
