Triethylamine → 4-(3-Fluoro-benzyl)-7-[4-(5-fluoro-thiophene-2-carbonyl)-piperazin-1-yl]-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid isopropyl ester

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A solution of 4-(3-fluoro-benzyl)-5-oxo-7-piperazin-1-yl-4,5-dihydro-thieno[3,2-b]pyrdine-6-carboxylic acid isopropyl ester (20) (2 g, 4.65 mmol), HOBt (0.692 g, 5.12 mmol), EDC.HCl (0.982 g, 5.12), triethylamine (0.971 mL, 6.98 mmol) and 5-fluoro-thiophene-2-carboxylic acid (0.749 g, 5.12 mmol) was stirred overnight at room temperature. The solution was poured into 2.5% NaHCO3 solution and the solids formed were filtered, washed by cold water and air dried. The crude product was purified by flash chromatography eluting with 0-10% methanol in CH2Cl2 gradient to yield 2.16 g (83%) of 4-(3-fluoro-benzyl)-7-[4-(5-fluoro-thiophene-2-carbonyl)-piperazin-1-yl]-5-oxo-4,5-dihydro-thieno[3,2-b]pyrdine-6-carboxylic acid isopropyl ester. 1H-NMR (DMSO-d6) δ 1.29 (d, J=6.0 Hz, 6H), 3.37 (m, 4H), 3.79 (m, 4H), 5.10 (m, 1H), 5.38 (s, 2H), 6.80 (m, 1H), 7.07 (m, 3H), 7.28 (t, J=3.6 Hz, 1H), 7.32 (d, J=5.6 Hz, 1H), 7.37 (m, 1H), 8.02 (d, J=5.6 Hz, 1H); EIMS m/z 558 (M+1).

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