Diisopropylethylamine → (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-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 (100 mg, 0.37 mmol) and 1-(2-methoxy-ethyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 72, 0.054 g, 0.38 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.19 g, 0.44 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (0.19 mL, 1.1 mmol) dropwise and the resulting solution stirred at room temperature over night. The solution was diluted with methylene chloride, washed with a 1 N hydrochloric acid solution (15 mL), a saturated sodium chloride solution (20 mL) dried over magnesium sulfate. The mixture was filtered and evaporated and the resulting material purified via automated flash chromatography (Analogix, SF4-40 g column, 50-70% ethyl acetate/hexanes) to give (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (94 mg, 65%) as an off white solid: [α]29D=−62.6°, (C=0.31, chloroform); HR-ES(+) m/e calcd for C22H28N4O3 [M+Na]+ 419.2053, observed 419.2055; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.01-2.09 (m, 7H), 3.18 (s, 4H), 3.61 (t, J=5.28 Hz, 2H), 4.12 (t, J=5.13 Hz, 2H), 4.38-5.23 (m, 4H), 6.37 (d, J=2.11 Hz, 1H), 7.32-7.84 (m, 7H), 10.84 (s, 1H).

Provenance & Evidence