Oxalyl chloride → 2-[1-(4-Chlorophenyl)cyclopropanecarboxamido]-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

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To a solution of 1-(4-chlorophenyl)cyclopropanecarboxylic acid (K1, 131 mg, 0.666 mmol) in anhydrous methylene chloride (3 mL) was added oxalyl chloride (0.100 mL, 1.17 mmol) followed by 2 drops of N,N-dimethylformamide at room temperature under nitrogen. After stirring at room temperature for 1 h, the reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in anhydrous tetrahydrofuran (3 mL). To the resulting solution was added diisopropylethylamine (0.200 mL, 1.12 mmol) followed by a suspension of compound F4 (150 mg, 0.666 mmol) in anhydrous tetrahydrofuran (3 mL). After stirring at room temperature for 3 h, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography on silica gel eluting with methylene chloride to methanol/methylene chloride (1:19). Further purification by trituration with acetonitrile gave compound K2 as a light yellow solid (87 mg, 32%): 1H NMR (500 MHz, CDCl3) δ 11.79 (bs, 1H), 7.47-7.42 (s, 4H), 5.56 (bs, 2H), 3.57 (s, 2H), 2.82-2.77 (m, 4H), 2.62 (q, J=7.0 Hz, 2H), 1.78-1.74 (m, 2H), 1.20-1.12 (m, 5H). MS (M+H) 404.

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