Sodium Carbonate → HCID 59633032, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 5-(5-bromothiophen-2-yl)-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylate (480 mg, 1.3 mmol) and 3-(methylsulfonyl)phenylboronic acid (390 mg, 1.9 mmol) was suspended in THF (6 mL) with Na2CO3 (1.0 mL of a 2M aqueous solution, 2.0 mmol). The mixture was sparged with nitrogen for ˜10 minutes, treated with Pd(PPh3)4 (54 mg, 47 mol), and heated to 65° C. After 4 hours at 65° C. there was still starting methyl 5-(5-bromothiophen-2-yl)-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylate visible as evidenced by LC/MS. Additional palladium catalyst was added and heating was continued. After heating at 65° C. overnight the reaction mixture was concentrated under reduced pressure to afford a dark semi-solid that was triturated with EtOAc and filtered to remove the solids. The filtrate was concentrated under reduced pressure and purified by flash column chromatography eluting with a gradient from 0% to 50% MeCN/CH2Cl2 to afford methyl 5-(5-(3-(methylsulfonyl)phenyl)-thiophen-2-yl)-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylate (137 mg, 24% yield) as a mixture with triphenylphosphine oxide. This colorless film will be carried on to the Grignard addition without further purification.

Provenance & Evidence