Diisopropylethylamine → (S)-3-cyclopentyl-N-[1-(3-hydroxy-propyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

Participants

Reaction Steps

To a solution of (S)-3-cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared as in Example 9, 80 mg, 0.29 mmol) and 3-(3-amino-pyrazol-1-yl)-propan-1-ol (prepared as in US 20080021032, Example 23, 49 mg, 0.35 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.15 g, 0.35 mmol) in methylene chloride (8 mL) was added N,N-diisopropylethylamine (0.15 mL, 0.88 mmol) dropwise and the resulting solution stirred at room temperature for 4 h. The solution was diluted with methylene chloride, washed with a 1 N hydrochloric acid solution (25 mL), a saturated sodium bicarbonate solution (25 mL) dried over magnesium sulfate. The mixture was filtered and evaporated and the resulting material purified via automated flash chromatography (Analogix, SF4-12 g column, 50-70% ethyl acetate/hexanes) to afford (S)-3-cyclopentyl-N-[1-(3-hydroxy-propyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (28 mg, 24%) as an off white solid: HR-ES(+) m/e calcd for C22H28N4O3 [M+H]+ 397.2234, observed 397.2233; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.94-2.34 (m, 7H), 4.04 (t, J=6.79 Hz, 3H), 4.37-5.28 (m, 6H), 6.39 (s, 2H), 7.31-7.90 (m, 8H), 10.86 (s, 2H).

Provenance & Evidence