Methanol → HCID 69607376, compound

Participants

Reaction Steps

2-(2-Cyano-acetylamino)-4-iodo-5-methyl-thiophene-3-carboxylic acid ethyl ester (189 mg, 0.5 mmol) was cyclized by NaH in THF at room temperature for 12 h as described in Example 29D. After reaction was finished, methanol (2 mL) was added and the mixture was evaporated. The residue was purified on HPLC to give 4-hydroxy-3-iodo-2methyl-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-cabonitrile (38 mg, 22.9%). This compound (33 mg, 0.1 mmol) was taken up in a Smith Process Vial (2–5 mL), CuI (7.6 mg, 0.04 mmol), Pd(PPh3)2Cl2 (14 mg, 0.02 mmol), DMF (2 ml), diisopro pylamine (1 mL) and phenylacetylene (20.4 mg, 0.2 mmol) were then added sequentially. After degassed, the vial was sealed and stirred at 70° C. for 2 h. The resulting mixture was filtered and the solid was washed with methanol (5 mL×2). The combined organic layers were concentrated under vacuum and purification on HPLC to give title compound (20 mg, 65%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 11.0 (s, 1H), 7.52–7.38 (m, 5H), 2.44 (s, 3H, MS (ESI) m/e 307 (M+H)+, 305 (M−H)−.

Provenance & Evidence