Ethyl chloroformate → 1h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-3-[[2-(2-oxo-1-pyrrolidinyl)ethoxy]methyl]-,methyl ester

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Reaction Steps

To a stirring solution of methyl 3-[(dimethylamino)methyl]-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (1.04 g, 3.05 mmol) in DCM (16 mL) under nitrogen was added ethyl chloroformate (0.330 g, 3.05 mmol). The solution was stirred for 2 hours at room temperature. At this time, 1-(2-hydroxyethyl)pyrrolidin-2-one (1.57 g, 12.18 mmol), ethyl(diisopropyl)amine (1.97 g, 15.23 mmol), and DMF (16 mL) were added to the reaction and the reaction heated to 55° C. After stirring for 24 hours (55° C.) the reaction was judged to be complete by HPLC-MS analysis and the volatiles were removed in vacuo (ca. 2 torr) to give red oil. The crude material was diluted with EtOAc (40 mL) and washed with water (4×20 mL) and brine (20 mL). The organic phase was separated, dried (Na2SO4), and concentrated in vacuo to afford the target compound, which was purified by chromatography on a column of silica gel. Fractions were combined to afford 0.961 g (76% yield) of methyl 1-(4-fluorobenzyl)-3-{[2-(2-oxopyrrolidin-1-yl)ethoxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxylate as an off white solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.90-2.01 (m, 2H) 2.32 (t, J=8.10 Hz, 2H) 3.42-3.51 (m, 4H) 3.64 (t, J=5.27 Hz, 2H) 4.00 (s, 3H) 4.69 (s, 2H) 5.36 (s, 2H) 7.01 (t, J=8.57 Hz, 2H) 7.11-7.18 (m, 2H) 7.28 (s, 1H) 8.51 (s, 1H) 8.73 (s, 1H).

Provenance & Evidence