1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920122, compound

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask under argon was placed 3-bicyclo[2.2.1]hept-7-yl-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (32 mg, 0.085 mmol) in dichloromethane (5 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (16 μL, 0.094 mmol) and 1-hydoxybenzotriazole (12 mg, 0.089 mmol) and stirred at 25° C. for 2 h. After this time, 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in US20080021032, Example 80, 16 mg, 0.102 mmol) was added and stirred for 16 h at 25° C. The reaction was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL), a saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 20% ethyl acetate/hexanes to 80% ethyl acetate/hexanes) afforded 3-bicyclo[2.2.1]hept-7-yl-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (27 mg, 61%) as yellow foam: HR-ES-MS m/z calculated for C27H33N4O4Cl [M+H]+ 513.2263, observed 513.2263; 1H NMR (300 MHz, CDCl3) δ ppm 1.15 (s, 6H), 1.15-1.31 (m, 4H), 1.43-1.59 (m, 3H), 1.65 (d, J=8.5 Hz, 2H), 1.70-1.87 (m, 1H), 1.90-2.09 (m, 3H), 2.80 (br. s., 1H), 3.93 (s, 2H), 4.16 (d, J=18.1 Hz, 1H), 4.32 (d, J=18.1 Hz, 1H), 4.76 (t, J=7.7 Hz, 1H), 4.89 (s, 1H), 6.70 (s, 1H), 7.17-7.25 (m, 1H), 7.27-7.37 (m, 3H), 7.48 (d, J=8.2 Hz, 1H), 8.74 (br. s., 1H).

Provenance & Evidence