Diisopropylethylamine → tert-butyl (3R,4S,55)-4-[{N-[(1-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}cyclopentyl)carbonyl]-L-valyl}(methyl)amino]-3-methoxy-5-methylheptanoate

Participants

Reaction Steps

To #6 (287 mg, 0.801 mmol, 1 eq.) in dichloromethane (4 mL, 0.2 M) were added 1-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}cyclopentanecarboxylic acid (309 mg, 0.879 mmol, 1.1 eq.), diisopropylethylamine (281 μL, 1.60 mmol, 2 eq.) and HATU (376 mg, 0.960 mmol, 1.2 eq.). The mixture was stirred for 18 hours and diluted with ethyl acetate (15 mL). The reaction mixture was washed with 1 M aqueous hydrochloric acid solution (2×5 mL) and with brine (5 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography (Gradient: 0% to 60% ethyl acetate in heptane) to provide #27 (502 mg, 91%) as a white foam. LC-MS: m/z 692.3 [M+H+], 714.3 [M+Na+], 636.3 [(M-2-methylprop-1-ene)+H+], retention time=1.13 minutes; 1H NMR (400 MHz, DMSO-d6), characteristic signals: δ 7.89 (br d, J=7.4 Hz, 2H), 7.67-7.75 (m, 2H), 7.60 (br s, 1H), 7.38-7.44 (m, 2H), 7.30-7.36 (m, 2H), 7.21 (br d, J=8.8 Hz, 1H), 4.44-4.59 (m, 2H), 4.17-4.27 (m, 3H), 3.68-3.78 (br m, 1H), 3.21 (s, 3H), 2.88 (br s, 3H), 2.09-2.20 (m, 2H), 1.39 (s, 9H).

Provenance & Evidence