1,2-Dichloroethane → tert-Butyl ((S)-1-((R)-3,3-dimethyl-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,3-azasilolidin-1-yl)-3-(4-iodophenyl)-1-oxopropan-2-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-2-((tert-butoxycarbonyl)amino)-3-(4-iodophenyl)propanoic acid (0.77 g, 2.0 mmol) in DMF (4 mL) was added EDC (0.53 g, 2.8 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 5 min, followed by addition of 3H-[1,2,3]-triazolo[4,5-b]pyridin-3-ol (0.22 g, 1.6 mmol) and a solution of (R)-3,3-dimethyl-N—((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,3-azasilolidine-5-carboxamide HCl (0.53 g, 1.6 mmol) in DMF (3 mL) and DIEA (0.8 mL, 4.6 mmol). The resulting mixture was then stirred at rt for 1 h and diluted with ethyl acetate and brine. The organic layer was separated, washed with aq. NaHCO3 solution, dried over MgSO4 and concentrated in vacuo. The resulting oil was purified by flash chromatography (eluting with 20% EtOAc/DCM) to afford the title compound as a white solid (0.94 g, 87%). 1H NMR (CDCl3) δ 7.76-7.45 (m, 2H), 7.22-7.05 (m, 3.5H), 6.89 (d, J=8.1 Hz, 2H), 6.50 (d, J=8.1 Hz, 0.5H), 5.27-5.06 (m, 3H), 4.96-4.71 (m, 1H), 3.10 (d, J=13.4 Hz, 0.5H), 2.96-2.45 (m, 4.5H), 2.16-1.98 (m, 1H), 1.85 (dd, J=11.3, 5.8 Hz, 3H), 1.44-1.16 (m, 10H), 0.98 (dd, J=14.7, 10.1 Hz, 1H), 0.44 (s, 3H), 0.27 (s, 3H); MS(ESI+) m/z 662.4 (M+H)+.

Provenance & Evidence