反应详情

To a solution of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (0.96 g, 1.70 mmol) and (S)-tert-butyl 2-amino-5-guanidinopentanoate (0.54 g, 1.79 mmol) in DMF (4 mL) at 0° C. was added HATU (0.69 g, 1.79 mmol) and DIPEA (0.82 mL, 5.27 mmol). The reaction was stirred at room temperature for 1 h, quenched with satd NaHCO3 and diluted with EtOAc. The mixture was washed with water (10 mL), brine (10 mL) and dried with Na2SO4. The residue was purified by column chromatography (silica, MeOH/DCM) to afford (S)-tert-butyl 2-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)-5-guanidinopentanoate (1.2 g) as a white solid. The solids were dissolved in 4N HCl in dioxane (8 mL) and stirred for 3 h. The reaction was concentrated and purified by chromatography (silica, MeOH/DCM) to yield the title compound (380 mg) as a white solid. 1H-NMR (DMSO-d6, 400 MHz) δ 8.84 (d, J=7.6 Hz, 1H), 7.81 (s, 1H), 7.64-7.61 (m, 1H), 7.46-7.43 (m, 1H), 7.21 (d, J=8.30 Hz, 1H), 7.18 (s, 1H), 7.01-6.93 (m, 2H), 6.61-6.57 (m, 1H), 6.54-6.49 (m, 3H), 4.37-4.31 (m, 1H), 4.07 (s, 2H), 3.68 (s, 3H), 3.15-3.11 (m, 2H), 1.88-1.70 (m, 2H), 1.61-1.54 (m, 2H), 1.47-1.46 (m, 6H), 1.42 (s, 9H); MS (EI) m/z 719 [MH]+.

1. customquenched with satd NaHCO3
2. additiondiluted with EtOAc
3. washThe mixture was washed with water (10 mL), brine (10 mL)
4. dry with materialdried with Na2SO4
5. customThe residue was purified by column chromatography (silica, MeOH/DCM)