2-Thiophenecarboxylic acid → HCID 11489938, compound

Participants

Reaction Conditions

Reaction Steps

A Smith Process Vial (2-5 mL) was charged with a stir bar and PS-Carbodiimide resin (108 mg, 0.12 mmol.). To the vessel were added thiophene-2-carboxylic acid (5.6 mg, 0.044 mmol.) d in 0.2 mL dimethyl acetamide, 1-hydroxybenzotriazole hydrate (5.4 mg, 0.04 mmol.) in 0.5 mL acetonitrile (acetonitrile), diisopropylethylamine (16.7 mg, 0.12 mmol.) in 0.5 mL acetonitrile and the product of Example 23S (19.6 mg, 0.04 mmol.) in 0.7 mL acetonitrile. The reaction vessel was sealed and heated to 100° C. for 300 seconds in an Ermys Optimizer. After cooling the reaction mixture was transferred to a pre-packed 1 g column of Si-Carbonate (>4 eq. of functionalized reagent), which had been previously conditioned with methanol. The reaction products were collected, and the solvents were evaporated. The crude residue was dissolved in 1:1 dimethyl sulfoxide/methanol and purified by reverse phase HPLC to give 8.7 mg (35%) of the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 0.83 (s, 9 H), 1.55-1.76 (m, 2 H), 2.64-2.83 (m, 4 H), 3.55 (s, 3 H), 3.60 (t, J=6.26 Hz, 1 H), 3.88 (s, 1 H), 4.18 (d, J=7.63 Hz, 1 H), 4.29 (s, 1 H), 7.01-7.25 (m, 12 H), 7.54 (d, J=8.85 Hz, 1 H), 7.60 (d, J=3.66 Hz, 1 H), 7.66-7.68 (m, 1 H), 8.18 (d, J=8.85 Hz, 1 H).

Provenance & Evidence