Reaction Steps
A solution of 2-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide (0.45 g, 0.9 mmol) in anhydrous DMF (10 ml) was treated with HBTU (0.48 g, 1.2 mmol), 2-(3-(methylcarbamoyl)piperidin-1-yl)acetic acid (0.20 g, 0.99 mmol) and diisopropylethyl amine (0.47 mL, 2.7 mmol) with stirring at room temperature overnight. To the reaction was added ethyl acetate (100 mL) and the mixture was washed with aqueous saturated sodium bicarbonate (100 mL×3). The organic layer was dried over magnesium sulfate, filtered and evaporated to a sticky yellow residue, 0.63 g that was purified by chromatography (silica gel, dichloromethane and methanol gradient) to afford 1-(2-(2-((2,4-dichloro-3-((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yloxy)methyl)phenyl)(methyl)amino)-2-oxoethylamino)-2-oxoethyl)-N-methylpiperidine-3-carboxamide (35) as a white solid, 0.17 g (28%), that was pure by LC/MS (+APCI) m/z 682 (M++1), 1HNMR (400 MHz, CDCl3) δ 8.60 (m, 1H), 7.60 (m, 2H), 7.50 (m, 1H), 7.30 (m, 1H), 7.35 (m, 1H), 7.19 (m, 1H), 7.04 (m, 1H), 6.92 (m, 1H), 6.81 (m, 2H), 6.70 (broad m, 1H), 5.67 (s, 2H), 5.29 (s, 2H), 4.21 (two s, 3H), 4.1 to 1.4 (many multiplets, 19H). 13CNMR (100 MHz, CDCl3) δ 174.4, 170.5, 168.8, 156.8, 156.1, 149.6, 149.0, 138.4, 138.2, 137.0, 136.5, 135.8, 135.3, 130.3, 122.6, 121.7, 120.8, 107.3, 103.1, 67.0, 61.6, 57.5, 56.5, 56.2, 54.3, 53.4, 47.7, 45.4, 41.3, 36.0, 30.9, 26.3, 26.1, 24.5. Anal. Calcd for C33H37Cl2N6O5+0.57CH2Cl2: C, 55.16; H, 5.26; N, 13.41. Found: C, 55.18; H, 5.14; N, 13.35.
