反应详情

To a solution of t-butyl (2S,3S)-3-methyl-1-((2R)-2-(4-(2-methylpentyloxy)phenyl)-2-((S)-2-phenylpropanamido)ethylamino)-1-oxopentan-2-ylcarbamate (80 mg, 0.138 mmol) in dichloromethane (2 mL) was added TFA (1 mL, 12.98 mmol). The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated and the residue was transferred to a separatory funnel containing saturated aqueous K2CO3 solution. The aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. 1H NMR indicated that the product was still a TFA salt. The product was dissolved in methanol and passed through a cation exchange resin (washed with methanol and water to remove the acid followed by 2M ammonia in methanol to elute the product) to afford (2S,3S)-2-amino-3-methyl-N-((2R)-2-(4-(2-methylpentyloxy)phenyl)-2-((S)-2-phenylpropanamido)ethyl)pentanamide (51 mg, 77% yield) as a colorless solid as the free base: 1H NMR (400 MHz, CDCl3) δ 7.70 (t, J=6.2 Hz, 1H), 7.26-7.33 (m, 2H), 7.19-7.26 (m, 3H), 6.93 (d, J=6.5 Hz, 1H), 6.87 (d, 2H), 6.70 (d, J=8.6 Hz, 2H), 4.89 (ddd, J=9.5, 6.4, 3.5 Hz, 1H), 3.72 (dd, J=8.8, 5.8 Hz, 1H), 3.62 (dd, J=8.8, 6.8 Hz, 1H), 3.45-3.57 (m, 2H), 3.35 (ddd, J=14.0, 5.7, 3.9 Hz, 1H), 3.23 (d, J=3.5 Hz, 1H), 1.93-2.04 (m, 1H), 1.83-1.93 (m, 1H), 1.42 (d, J=7.1 Hz, 3H), 1.23-1.54 (m, 6H), 1.01-1.21 (m, 2H), 0.96 (d, J=6.8 Hz, 3H), 0.94 (d, J=7.3 Hz, 3H), 0.90 (t, J=7.3 Hz, 3H), 0.89 (t, J=7.1 Hz, 3H); LRMS (ESI) m/e 482.5 [(M+H)+, calcd for C29H44N3O3 482.3].

1. concentrationThe mixture was concentrated
2. customthe residue was transferred to a separatory funnel
3. additioncontaining saturated aqueous K2CO3 solution
4. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
5. dry with materialThe combined organic layers were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe product was dissolved in methanol
9. washwashed with methanol and water
10. customto remove the acid
11. washto elute the product)