Dabco → 7-Benzyl-6-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

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Reaction Conditions

Reaction Steps

Oxalyl chloride (0.66 mL, 0.008 mol) was added slowly to a solution of 7-benzyl-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester (60) (1.0 g, 0.003 mol) in 25 mL anhydrous DMF stirred at −45° C. under argon. The solution was heated to 70° C. for 4 hours, and then poured into water. A small amount of brine was added, and the precipitated solid was collected by vacuum filtration. The oily solid was dissolved in dichloromethane, dried with magnesium sulfate, and then concentrated under vacuum to yield an oil. The oil was dissolved in DMF. Piperazin-1-yl-thiophen-2-yl-methanone (1.2 g, 0.004 mol) and DABCO (0.68 g, 0.006 mol) were added to the solution under argon. The solution was heated to 110° C. for 5 hours, and then poured into a 5% ammonium chloride aqueous solution. The precipitated solid was collected by vacuum filtration, and then purified by reverse phase (MeCN/water) chromatography to yield 0.320 g (21%) of 7-benzyl-6-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester. 1H-NMR (DMSO-d6) δ 1.28 (t, J=7.2 Hz, 3H), 3.40 (b, 4H), 3.81 (b, 4H), 4.26 (q, J=7.2 Hz, 2H), 5.26 (s, 2H), 7.15 (m, 1H), 7.28 (m, 5H), 7.35 (m, 2H), 7.47 (m, 1H), 7.79 (m, 1H) ppm; EIMS m/z 508 (M+1).

Provenance & Evidence