Diisopropylethylamine → HCID 57920135, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of (S)-2-amino-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]amide hydrochloride salt (2.0 g, 5.8 mmol) in acetonitrile (25 mL) was treated with N,N-diisopropylethylamine (4.0 mL) and stirred at 60° C. for 15 min. At this time N,N-diisopropylethylamine (2.5 mL) and a solution of (E)-4-bromo-3-(3-ethoxy-2,6-difluoro-phenoxy)-but-2-enoic acid ethyl ester (prepared in Example 116, 1.37 g, 3.75 mmol) in acetonitrile (10 mL) were added and the resulting solution refluxed for 48 h. The mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The layers were separated and the organic layer was dried over sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue purified by ISCO flash chromatography (RediSep silica 40 g, 5% to 80% (10% methanol/dichloromethane)/hexanes) which afforded (S)-2-[4-(3-ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (295 mg, 16%): HR-ES-MS (m/z) calculated for C25H32F2N4O5 [M+H]+ 507.2414, observed 507.2414; 1H NMR (300 MHz, CDCl3) δ ppm 0.96 (br. s., 6H), 1.13 (br. s., 6H), 1.42 (br. s., 3H), 1.48-1.64 (m, 1H), 1.66-1.95 (m, 2H), 3.73 (br. s., 1H), 3.91 (br. s., 2H), 4.01-4.24 (m, 3H), 4.38 (d, J=17.8 Hz, 1H), 4.88 (br. s., 1H), 4.99 (br. s., 1H), 6.66 (br. s., 1H), 6.73-7.00 (m, 2H), 7.27 (br. s., 1H), 8.79 (br. s., 1H).

Provenance & Evidence