Ethyl Acetate → HCID 178442397, compound

Participants

Reaction Steps

A mixture of 5-(3,3-Dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (78 mg, 0.175 mmol) and 2-fluoro-pyridine (145 μL, 1.68 mmol) in DMF (0.6 mL) was treated with sodium hydride (67 mg, 1.68 mmol, 60% oil dispersion) in two or three portions. The mixture was stirred until the bubbling slowed, and was sealed and heated by microwave at 100 deg C. for 30 min. After cooling, ethyl acetate (2-3 mL) was added and the mixture was carefully quenched with citric acid (10% aqueous solution, 2-3 mL). Water was added and the mixture was extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by HPLC (Gemini column, 35% acetonitrile:water, 2 min, 35-50% acetonitrile:water, 2 min, 50-95% acetonitrile:water 13 min, both solvents containing 0.1% trifluoroacetic acid). This resulted in 65 mg (58% yield) of the title compound as a white powder (TFA salt): MS (m/z): 520.9 [M−H]−; HPLC retention time: 4.61 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Provenance & Evidence