To a mixture of Example 83B (100 mg, 0.296 mmol), triethylamine (0.091 mL, 0.652 mmol), and acetic acid (0.085 mL, 1.482 mmol) in dichloromethane (3 mL) was added (S)-tert-butyl 2-amino-3,3-dimethylbutanoate hydrochloride (133 mg, 0.593 mmol) and MP-(CN)BH3 resin (Biotage, 2.17 mmol/g, 546 mg, 1.186 mmol). The reaction mixture was shaken on an orbital shaker overnight. The reaction mixture was diluted with 5 mL dichloromethane and the resin filtered off, rinsing with dichloromethane and methanol. The crude material was purified via column chromatography: Analogix Intelliflash™ 280, 12 g silica cartridge, 0-4% methanol/dichloromethane gradient over 30 minutes. The material was dissolved in 5 mL dichloromethane and treated with excess trifluoroacetic acid and stirred at room temperature overnight. The volatiles were removed in vacuo, the residue was dissolved in 5 mL methanol, and the mixture was treated with excess 2 M HCl/diethyl ether. The solution was stirred at room temperature for 20 minutes and then diluted with diethyl ether. The resultant solid was collected by filtration and dried under high vacuum to give the title compound as a hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) δ 13.34 (s, 1H) 8.80-9.10 (m, 3H) 8.36 (s, 1H) 7.46-7.57 (m, 2H) 7.27-7.39 (m, 1H) 6.60-6.78 (m, 2H) 4.02 (d, J=10.07 Hz, 1H) 3.76-3.88 (m, 3H) 3.51-3.61 (m, 1H) 3.15-3.36 (m, 2H) 2.57-2.93 (m, 2H) 2.34 (s, 1H) 1.99-2.16 (m, 1H) 1.78-1.98 (m, 1H) 1.15 (s, 9H). MS (ESI+) m/z 453.2 (M+H)+.
