To (2S,3S)-2-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)-3-(4-(trifluoromethyl)phenyl)butanoic acid (0.11 g, 0.23 mmol) in 3 mL of DMF was added EDCI (0.065 g, 0.34 mmol) and HOBt (0.062 g, 0.46 mmol). After 10 minutes, 5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine (0.057 g, 0.25 mmol) was added. 5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine was prepared as shown in Scheme 5 using isoquinoline-6-carboxylic acid, commercially available from AstaTech Product List (Order Number 62874), instead of 4-chlorothieno[2,3-c]pyridine-2-carboxylic acid. The mixture was stirred for 12 hours. The solvent was removed under reduced pressure and the residue was taken up in 20 mL of EtOAc. The mixture was washed with aq NH4Cl (5 mL), water (5×5 mL), and brine (5 mL), then dried over MgSO4. The mixture was filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluting with a gradient from 0 to 2.5% MeOH in DCM) to provide tert-butyl (2S,3S)-4-(tert-butyldimethylsilyloxy)-1-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylamino)-1-oxo-3-(4-trifluoromethylphenyl)butan-2-ylcarbamate (0.086 g, 54%) as a yellow solid. 1H NMR (400 MHz, CD3OD): δ ppm 9.38 (s, 1H), 8.61-8.58 (m, 2H), 8.40 (d, J=8.9, 1H), 8.32 (d, 8.6 Hz, 1H), 8.06 (s, 1H), 8.04 (d, J=5.8 Hz, 1H), 7.70 (d, J=7.9 Hz, 2H), 7.61 (d, J=8.1 Hz, 2H), 5.01-4.95 (m, 1H), 4.11-3.96 (m, 2H), 3.62-3.55 (m, 1H), 1.38 (s, 9H), 0.87 (s, 9H), 0.02 (s, 3H), 0.00 (s, 3H). 1H not detected.
