Diisopropylethylamine → HCID 86706126, compound

Participants

Reaction Steps

To a solution of (E)-(S)-4-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-2-methoxymethyl-2-methyl-but-3-enoic acid (176 mg, 0.34 mmol) in dichloromethane (2 mL), was added (S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (205 mg, 0.47 mmol), 4-dimethylaminopyridine (116 mg, 0.95 mmol), N,N-diisopropylethylamine (123 mg, 0.95 mmol) and 2-methyl-6-nitrobenzoic anhydride (164 mg, 0.47 mmol). The reaction mixture was stirred at room temperature for 18 h, was then treated with saturated solution of sodium hydrogen carbonate, extracted with dichloromethane (2×) and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated. The crude residue was purified by silica gel chromatography using a Biotage KP-Sil 50 g cartridge eluting with a gradient of iso-hexanes/ethyl acetate 9:1 to 0:1 to give the title product (0.22 g, 78%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 0.85-1.10 (m, 6H), 1.20-1.70 (m, 23H), 2.05-2.20 (m, 1H), 2.30-2.45 (m, 1H), 3.44 (s, 3H), 3.60-3.95 (m, 4H), 4.15-4.32 (m, 1H), 4.68-4.70 (m, 1H), 4.90-5.05 (m, 2H), 5.20-5.45 (m, 1H), 6.10-6.28 (m, 1H), 6.60-6.85 (m, 2H), 7.10-7.20 (m, 1H), 7.28 (d, J=8.4 Hz, 1H), 7.66-7.74 (m, 2H), 8.00 (d, J=4.0 Hz, 1H), 8.05 (d, J=8.4 Hz, 1H). LCMS (m/z) 828.5 [M+H], Tr=3.48 min.

Provenance & Evidence