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 (prepared as in Example 9, 94 mg, 0.35 mmol) and 1-(2-isopropoxy-ethyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 101, 70 mg, 0.41 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.18 g, 0.41 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (0.18 mL, 1.0 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% ethyl acetate/hexane) to afford (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (110 mg, 75%) as an off white solid: [α]31D=−50.6°, (c=0.36, chloroform); HR-ES(+) m/e calcd for C24H32N4O3 [M+H]+ 425.2547, observed 425.2547; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.77-2.18 (m, 17H), 3.40-5.25 (m, 8H), 6.39 (d, J=2.11 Hz, 1H), 7.26-7.91 (m, 5H), 10.86 (s, 1H).

Provenance & Evidence