反应详情

To a solution of 3-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoic acid (intermediate XI, 10.0 mg, 0.019 mmol) and (2,2,2-trifluoro-1-phenylethyl)amine (7.6 mg, 0.056 mmol) in DMF (500 μL) were added BOP reagent (10.0 mg, 0.022 mmol), ethyl(diisopropyl)amine (5.0 μL, 0.028 mmol). After sitting at rt for 4 hr, the reaction was purified by preparative HPLC (5->95% CH3CN/H2O, 0.1% added TFA, C18 PRO YMC 20×150 mm) to afford tert-butyl {1-benzyl-1-methyl-2-[(3-[(methylsulfonyl)(propyl)amino]-5-{[(2,2,2-trifluoro-1-phenylethyl)amino]carbonyl}benzyl)oxy]ethyl}carbamate which was taken up in HCl(g) saturated EtOAc (1 mL). After 15 hr, it was purified by preparative HPLC (5->95% CH3CN/H2O, 0.1% added TFA, C18 PRO YMC 20×150 mm) to provide 3-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-5-[(methylsulfonyl)(propyl)amino]-N-(2,2,2-trifluoro-1-phenylethyl)benzamide as a white solid. 1H NMR (400 MHz, CD3OD) δ 7.90 (s, 1H), 7.84 (s, 1H), 7.65 (s, 1H), 7.61-7.55 (m, 2H), 7.46-7.40 (m, 3H), 7.34-7.24 (m, 3H), 7.20-7.15 (m, 2H), 6.04-5.96 (m, 1H), 4.72 (A of AB, d, J=13.8 Hz, 1H), 4.68 (B of AB, d, J=13.8 Hz, 1H), 3.71 (t, J=7.1 Hz, 2H), 3.45 (A of AB, d, J=10.0 Hz, 1H), 3.40 (B of AB, d, J=10.0 Hz, 1H), 3.08 (A of AB, d, J=13.4 Hz, 1H), 2.96 (s, 3H), 2.87 (B of AB, d, J=13.4 Hz, 1H), 1.51-1.41 (m, 2H), 1.25 (s, 3H), 0.90 (t, J=7.4 Hz, 3H).

1. customthe reaction was purified by preparative HPLC (5->95% CH3CN/H2O, 0.1%
2. additionadded TFA