Methanol → Methyl 6-(4-{1,2-dimethyl-1-[5-(pyridin-2-ylmethoxy)pyridin-2-yl]propyl}phenyl)pyridazine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

Palladium (II) acetate (8.00 mg, 0.0350 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (39.0 mg, 0.070 mmol) were added successively to a stirred solution of 5b (155 mg, 0349 mmol) in triethylamine:DMF:MeOH (4.00 mL of a 1:10:10 mixture, respectively) at rt. A gentle stream of the carbon monoxide gas was bubbled through the reaction mixture for approximately 15 min, after which the resulting mixture was heated to 70° C. under a carbon monoxide atmosphere (balloon) for about 5 h. After cooling to rt, the reaction mixture was filtered through a short column of CELITE®, eluting with DCM. The filtrate was partially concentrated in vacuo and diluted with EtOAc. The organic phase was washed with water, brine, dried (sodium sulfate) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 30%-100% EtOAc/hexanes as eluent) afforded the title compound 5c. m/z (ES) 469 (MH)+. 1HNMR (500 MHz, CDCl3): δ 8.62 (d, 1H, J=4.8 Hz), 8.41 (m, 1H), 8.22 (d, 1H, J=8.7 Hz), 8.08 (d, 2H, J=8.8 Hz), 7.96 (d, 1H, J=8.9 Hz), 7.75 (dt, 1H, J=1.7, 7.7 Hz), 7.56 (d, 2H, J=8.7 Hz), 7.53 (d, 1H, J=7.8 Hz), 7.26 (dd, 1H, J=5.2, 7.3 Hz), 7.19 (m, 2H), 5.23 (s, 2H), 4.10 (s, 3H), 3.11 (m, 1H, 6.6 Hz), 1.73 (s, 3H), 0.89 (d, 3H, J=6.7 Hz), 0.83 (d, 3H, J=6.8 Hz).

Provenance & Evidence