To a mixture of Example 241B (125 mg, 0.372 mmol), triethylamine (0.114 mL, 0.818 mmol), acetic acid (0.106 mL, 1.858 mmol) and (R)-tert-butyl 2-amino-3-methylbutanoate hydrochloride (0.401 mL, 1.858 mmol) in 4 mL 1:1 dichloromethane/methanol was added Biotage MP-cyanoborohydride resin (2.17 mmol/g, 678 mg, 1.487 mmol) and the mixture was shaken at room temperature overnight. The mixture was diluted with dichloromethane and the resin was filtered off, rinsing with dichloromethane and methanol. The crude material was purified by flash chromatography (Analogix280, eluting with a 0-4% methanol/dichloromethane gradient). The tert-butyl ester in 5 mL dichloromethane was treated with excess trifluoroacetic acid for 10 hours. The solvent was removed and the residue was dissolved in 5 mL methanol and treated with 2M hydrogen chloride in diethyl ether for 1 hour. The mixture was diluted with 50 mL diethyl ether and the solid was filtered and dried in vacuo to give the title compound as the hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) δ 0.87-1.16 (m, 6H) 1.76-2.02 (m, 1H) 2.09-2.40 (m, 2H) 2.56-2.87 (m, 3H) 3.20-3.45 (m, 1H) 3.64-3.86 (m, 3H) 4.05 (s, 1H) 6.40 (s, 1H) 6.60 (s, 1H) 7.13-7.44 (m, 4H) 8.22-8.33 (m, 1H) 8.40 (d, J=1.83 Hz, 1H) 8.65-9.88 (m, 2H) 12.70 (d, J=3.97 Hz, 1H). MS (ESI): 438.1 (M+H)+.
