Dimethylformamide → HCID 58212052, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of Compound 18 (6.0 g, 15.0 mmol), 3-amino-6-chloropyridazine (3.0 g, 22.5 mmol) and cesium carbonate (14.7 g, 45.0 mmol) were added DMF (140 mL) and water (35 mL). The reaction solution was flushed with argon for 10 min, and then dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (1.2 g, 1.5 mmol) was added. The resultant mixture was flushed with argon for 5 min and heated at 80° C. for 1 h. The reaction solution was then cooled to room temperature, diluted with ethyl acetate, washed with 1:1 brine and water (2×), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography (92:2:5.4:0.6 to 47:47:5.4:0.6 dichloromethane/ethyl acetate/methanol/concentrated ammonium hydroxide) to give rac-1 (3.2 g, 58%) as a light tan solid: 1H NMR (500 MHz, CDCl3) δ 7.82-7.76 (m, 4H), 7.71 (s, 1H), 7.61-7.57 (m, 2H), 7.47-7.43 (m, 2H), 7.30 (dd, J=8.0, 1.5 Hz, 1H), 6.99 (d, J=8.0 Hz, 1H), 6.80 (d, J=9.5 Hz, 1H), 4.71 (br s, 2H), 4.50 (t, J=7.0 Hz, 1H), 3.89 (d, J=15.0 Hz, 1H), 3.74 (d, J=14.5 Hz, 1H), 3.14 (dd, J=11.5, 6.0 Hz, 1H), 2.70 (dd, J=11.5, 9.0 Hz, 1H), 2.48 (s, 3H); ESI MS m/z 367 [M+H]+.

Provenance & Evidence