Diisopropylethylamine → HCID 70674449, compound

Participants

Reaction Steps

To a solution of (S)-3-cyclopropyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (85 mg, 0.35 mmol) and 1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 94, 64 mg, 0.38 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.18 g, 0.42 mmol) in methylene chloride (8 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, SF4-40 g column, 50-70% ethyl acetate/hexanes) to give (S)-3-cyclopropyl-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (46 mg, 34%) as an off white solid: [α]30D=−38.1°, (c=0.21, chloroform); HR-ES(+) m/e calcd for C22H28N4O3 [M+H]+ 397.2234, observed 397.2235; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.03-1.69 (m, 9H), 2.00-2.28 (m, 1H), 3.15 (s, 4H), 3.99 (s, 2H), 4.36-5.39 (m, 4H), 6.42 (d, J=1.81 Hz, 1H), 7.25-7.88 (m, 6H), 10.80 (s, 1H).

Provenance & Evidence