Diisopropylethylamine → 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid (31 mg, 0.072 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 20 mg, 0.086 mmol) in N,N-dimethylformamide (1 mL). To this mixture was added N,N-diisopropyethylamine (35 μL, 0.22 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (48 mg, 0.11 mmol) and stirred overnight at 25° C. After this time, the mixture was diluted with ethyl acetate (15 mL) and washed with a saturated aqueous solution of ammonium chloride (10 mL), saturated aqueous solution of sodium bicarbonate (10 mL) and a saturated aqueous solution of sodium chloride (10 mL), dried over sodium sulfate, and concentrated with silica gel (1.5 g). Purification by Biotage flash chromatography (AnaLogix 12 g column, 40% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-4-trifluoromethyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (34 mg, 77%) as a cream colored foam: HR-ES-MS m/z calculated for C25H25N4O5ClF6 [M+H]+ 611.1491, observed 611.1487.

Provenance & Evidence