Pyrrolidine → 1-(4-Methoxy-phenyl)-6-(2-oxo-2-pyrrolidin-1-yl-ethyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

Participants

Reaction Conditions

Reaction Steps

Part A: Pyrrolidine (0.152 mL, 1.826 mmol) was dissolved in methylene chloride (6 mL) and cooled to 0° C. 2M Trimethylaluminum (0.652 mL, 1.304 mmol) was added to the reaction and stirred for 30 min at 0° C. [1-(4-Methoxy-phenyl)-7-oxo-3-trifluoromethyl-1,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridin-6-yl]-acetic acid methyl ester (0.100 g, 0.261 mmol) was added and the reaction was stirred overnight at rt. The reaction was quenched with water (100 mL), extracted into methylene chloride (3×50 mL), washed with brine (1×50 mL), dried over MgSO4, concentrated, and purified, by flash chromatography using 0–100% ethyl acetate/hexanes gradient and methanol flush as eluents, followed by further purification by reverse phase HPLC. Freeze-drying afforded 0.052 g (47%): 1H NMR (CDCl3) δ 7.38 (d, j=8.8 Hz, 2H), 6.87 (d, j=9.1 Hz, 2H), 4.15 (s, 2H), 3.77 (t, j=6.8 Hz, 2H), 3.76 (s, 3H), 3.40(t, j=6.8 Hz, 2H), 3.33 (t, j=6.8 Hz, 2H), 3.00(t, j=6.8 Hz, 2H), 1.92–1.85 (m, 2H), 1.82–1.73 (m, 2H) ppm; Mass Spec 423.3(M+H)+.

Provenance & Evidence