1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(3-((3,5-Dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxyphenylsulfonamido) methyl)benzyl)-N-isobutyl-6-(piperidin-1-yl)nicotinamide

Participants

Reaction Steps

3,5-Dichloro-N-((4′-fluorobiphenyl-4-yl)methyl)-2-hydroxy-N-(3-((isobutyl amino)methyl)benzyl)benzene sulfonamide (Compound E of Example 184, 0.04 g, 0.066 mmol, 1 eq) was dissolved in acetonitrile. DIPEA (0.034 mL, 0.198 mmol, 3 eq) was added followed by 6-(piperidin-1-yl)nicotinic acid (0.013 g, 0.066 mmol, 1 eq), EDCI (0.018 g, 0.099 mmol, 1.5 eq) and HOBT (0.013 g, 0.099 mmol, 1.5 eq). The reaction mixture was stirred at ambient temperature for 12 h and concentrated to remove the volatiles. The residue obtained was dissolved in ethyl acetate. The organic layer was washed with water, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford the title compound (0.03 g, 60%). 1H NMR (400 MHz, DMSO-d6) δ 0.74 (t, 6H), 1.50-1.59 (m, 6H), 1.9-2.0 (s, 1H), 3.03-3.04 (t, 2H), 3.54-3.55 (t, 4H), 4.45-4.49 (m, 6H), 6.82-6.84 (d, 1H), 6.9 (t, 1H), 7.03-7.05 (m, 2H), 7.14-7.28 (m, 6H), 7.42-7.44 (d, 2H), 7.53-7.61 (m, 4H), 7.80 (s, 1H), 8.12 (s, 1H). MS (ESI): 788.6 (M−H)−.

Provenance & Evidence