反应详情

To a solution of (S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared as in Example 1, 71 mg, 0.21 mmol) and 1-(2-methoxy-ethyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 72, 32 mg, 0.23 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.11 g, 0.25 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (0.11 mL, 0.62 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 bicarbonate solution (20 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, 50-80% ethyl acetate/hexanes) to give (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide (42 mg, 43%) as an off white solid: HR-ES(+) m/e calcd for C23H27N4O3F3 [M+H]+ 465.2108, observed 465.2107; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04-2.18 (m, 10H), 3.20 (s, 3H), 3.51-4.28 (m, 4H), 4.60-5.34 (m, 3H), 6.40 (d, J=1.81 Hz, 1H), 7.41-8.28 (m, 5H), 10.93 (s, 1H).

1. washwashed with a 1 N hydrochloric acid solution (15 mL)
2. dry with materiala saturated sodium bicarbonate solution (20 mL) dried over magnesium sulfate
3. filtrationThe mixture was filtered
4. customevaporated
5. customthe resulting material purified