Pyrazole → HCID 59363685, compound

Participants

Reaction Conditions

Reaction Steps

DMF (1.5 ml) was added to a mixture of methyl 3-iodo-6-methyl-2-pyridinecarboxylate D36 (200 mg), 1H-pyrazole (98 mg, 1.444 mmol), (1R,2R)—N,N-dimethyl-1,2-cyclohexanediamine (20.54 mg, 0.144 mmol), bis(copper(I) trifluoromethanesulfonate), benzene complex (18.17 mg, 0.036 mmol) and cesium carbonate (470 mg, 1.444 mmol) in a screw-topped vial. The mixture was degassed via 3 vacuum/nitrogen cycles and heated with shaking to 120° C. for 1 hour. The reaction mixture was evaporated to dryness under reduced pressure. The residue was dissolved in water/MeOH (1:1, 3 ml) and acidified to pH=2 by addition of 4 M HCl solution. The resulting mixture was evaporated to dryness under reduced pressure then the residue was triturated with DCM/MeOH (3:1, 20 ml). The mixture was filtered washing with more DCM/MeOH (3:1, 5 ml). The filtrate was treated with TMS-diazomethane solution (2 M in hexanes, 2 ml, 4 mmol) to re-esterify the acid. The reaction mixture was evaporated under reduced pressure and the residue was purified twice by flash chromatography on silica gel (Biotage Snap 10 g column, EtOAc/Cy from 20/80 to 50/50 and then Biotage KP-NH Snap 11 g column, EtOAc/DCM isocratic 1/99) to give the title compound D37 (107 mg) as a colourless gum.

Provenance & Evidence