Reaction Steps
A solution of tert-butyl 3-((2-((2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)(methyl)amino)-2-oxoethyl)carbamoyl)-[1,3′-bipyrrolidine]-1′-carboxylate (0.27 g, 0.35 mmol) in dichloromethane (10 ml) was cooled in an ice bath and treated with dropwise addition of trimethylsilyl triflate (0.07 mL, 0.39 mmol) and stirred at 0° C. for ten minutes. The reaction was treated with another dropwise addition of trimethylsilyl triflate (0.06 mL, 0.35 mmol) stirring at 0° C. for one hour. The reaction was quenched with triethyl amine (1 mL), evaporated, treated with aqueous saturated sodium bicarbonate (10 mL) and brine (100 mL) and extracted with dichloromethane (100 mL×3). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to afford N-(2-((2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)(methyl)amino)-2-oxoethyl)-[1,3′-bipyrrolidine]-3-carboxamide (22) as a tan solid, 0.22 g (94%), that was about 90% pure by LC/MS (+ESI) m/z 666 (M++1) with about 10% impurity of MW 786 (M+). 786 (M++1). 1HNMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.93 (m, 1H), 7.59 (m, 1H), 7.45 (m, 1H), 7.32 (m, 1H), 7.19 (m, 1H), 7.04 (m, 1H), 6.95 to 2.00 (many m, 17H). 13CNMR (100 MHz, CDCl3) δ 175.6, 169.5, 169.2, 156.9, 156.1, 149.6, 149.1, 138.4, 137.1, 136.4, 135.8, 135.4, 130.1, 129.8, 122.6, 121.7, 120.8, 107.4, 103.1, 67.1, 62.6, 57.5, 55.0, 54.9, 53.4, 51.4, 50.4, 47.7, 46.1, 44.0, 43.9, 41.9, 30.9, 9.0.
