1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask under argon was placed (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methoxy-butyric acid (62 mg, 0.19 mmol) in dichloromethane (5 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (37 μL, 0.21 mmol) and 1-hydoxybenzotriazole (27 mg, 0.20 mmol) and stirred at 25° C. for 2 h. After this time period, 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 45 mg, 0.23 mmol) was added and stirred for 16 h at 25° C. After this time, the reaction was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL) and a saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 50% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide (26 mg, 27%) as a colorless oil.

Provenance & Evidence