反应详情

Step O (1): (2R,3S)-1-((1S,3R)-3-(Allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-difluorophenyl)butan-2-ol (20 mg, 52.3 μmol) from step E (2), (S)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)pent-4-enoic acid (12.5 mg, 52.3 μmol) from step M (5), EDC (10 mg, 52.3 μmol), HOBt (7.1 mg, 52.3 μmol), DIEA (46.7 μL, 262 μmol) were mixed in 1 mL of DMF. The mixture was stirred at RT for 24 h. Purified with reverse phase Prep-HPLC to give 28.2 mg of (S)—N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-yl)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)pent-4-enamide as the TFA salt: LC-MS (M+H)+=603.3 HRMS (M+H)+=604.3755 1H NMR (500 MHz, CDCl3) 8 ppm 0.80-0.96 (m, 6H) 1.08 (dd, J=10.53, 8.70 Hz, 1H) 1.23-1.38 (m, 1H) 1.54-1.66 (m, 2H) 1.96-2.06 (m, 1H) 2.26-2.45 (m, 3H) 2.51-2.77 (m, 3H) 2.85-2.95 (m, 1H) 3.03-3.16 (m, 2H) 3.28 (d, J=11.90 Hz, 1H) 3.76-3.84 (m, 3H) 3.92 (d, J=1.83 Hz, 1H) 4.03-4.12 (m, 2H) 4.20-4.29 (m, 1H) 4.46 (dd, J=10.22, 5.34 Hz, 1H) 4.73 (d, J=6.41 Hz, 1H) 4.78-4.87 (m, 1H) 4.95-5.07 (m, 2H) 5.21 (d, J=10.38 Hz, 1H) 5.30 (dd, J=17.40, 1.53 Hz, 1H) 5.54 (dd, J=14.80, 7.78 Hz, 1H) 5.84-5.98 (m, 1H) 6.71 (s, 1H) 6.95 (dd, J=8.24, 2.14 Hz, 1H) 7.11-7.28 (m, 6H) 7.34 (d, J=8.24 Hz, 1H).

1. customPurified with reverse phase Prep-HPLC