Triethylamine → (s)-2-[4-(2,3-Dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-n-[1-(2-hydroxy-2-methyl-propyl)-1h-pyrazol-3-yl]-3-(tetrahydro-pyran-2-yl)-propionamide

Participants

Reaction Steps

(S)-2-amino-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydropyran-2-yl)-propionamide hydrochloride (118 mg, 0.30 mmol) was dissolved in methanol (2 mL) and triethylamine (0.2 mL) was added. The mixture was evaporated to dryness. The residue was dissolved in acetonitrile (5 mL). To this solution was added (E)-4-bromo-3-(2,3-dichloro-phenoxy)-but-2-enoic acid ethyl ester (prepared as in Example 77, 109 mg, 0.30 mmol). The mixture was refluxed for 40 h. The mixture was evaporated and the residue was treated with ethyl acetate and water. The layers were separated and the organic layer was dried over sodium sulfate and concentrated to give a crude product (180 mg). One part of the crude product (30 mg) was purified through reverse phase preparative HPLC (acetonitrile in water, 25% to 100% linear gradient) to afford (S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-2-yl)-propionamide as a white powder (6 mg): LR-ES-MS m/z calculated for C25H30Cl2N4O5 [M]+ 536, observed [M+H]+ 537; 1H-NMR (CDCl3) δ ppm 1.16 (s, 6H), 1.25-1.73 (m, 5H), 1.73-2.00 (m, 2H), 2.17-2.34 (m, 1H), 3.29-3.49 (m, 2H), 3.88-4.06 (m, 3H), 4.24 (d, J=17.8 Hz, 1H), 4.42 (d, J=17.8 Hz, 1H), 4.89 (s, 1H), 5.02-5.16 (m, 1H), 6.70 (br s, 1H), 7.14-7.23 (m, 1H), 7.28-7.37 (m, 3H), 7.42 (d, J=8.2 Hz, 1H), 8.76 (br s, 1H).

Provenance & Evidence