Reaction Steps
A solution of 3-[(dipropylamino)carbonyl]-5-(4-methyl-1,3-oxazol-2-yl)benzoic acid (77.5 mg, 0.23 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride (96 mg, 0.23 mmol), HOBt (32 mg, 0.23 mmol), and N-methylmorpholine (83 μL, 0.75 mmol) was stirred in dimethylformamide (2 mL) for 15 min. EDC (73 mg, 0.42 mmol) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with water, and extracted with ethyl acetate (3×25 mL). The organic layer was washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), saturated sodium chloride, dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(4-methyl-1,3-oxazol-2-yl)-N 3,N3-dipropylisophthalamide (40 mg): 1H NMR (300 MHz, CDCl3) δ 8.20 (br s, 1H, —NH), 8.17 (s, 1H), 8.05 (s, 1H), 7.52 (s, 1H), 7.38 (s, 1H), 7.24–7.08 (m, 5H), 7.02 (d, J=8 Hz, 2H), 6.61 (t, J=8 Hz, 1H), 4.27 (br s, 1H), 3.93 (d, J=4 Hz, 1H), 3.85 (s, 2H), 3.54 (br s, 2H), 3.43 (br s, 2H), 2.84 (d, J=5 Hz, 2H), 2.63 (q, J=8 Hz, 2H), 2.18 (s, 3H), 1.74 (t, J=5 Hz, 2H), 1.41 (d, J=7 Hz, 2H), 1.22 (t, J=8 Hz, 3H), 1.03 (t, J=7 Hz, 3H), 0.64 (t, J=7 Hz, 3H); ESI MS m/z 647 [M+H]+
