Cesium carbonate → 6-Chloro-2-methyl-4-({5-[(morpholin-4-yl)carbonyl]pyridin-2-yl}amino)-2,3-dihydropyridazin-3-one

Participants

Reaction Conditions

Reaction Steps

(6-Aminopyridin-3-yl)(morpholino)methanone (58 g, 280 mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (63.66 g, 285 mmol, Eq: 1.02) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.86 g, 8.4 mmol, Eq: 0.03) were dissolved in DMF (1.1 l) under heating. Cesium carbonate (274 g, 840 mmol, Eq: 3) was added. Finally Pd2 (dba)3 (3.84 g, 4.2 mmol, Eq: 0.015) was added under an argon atmosphere. The reaction mixture was heated to 93° C. (internal temperature) for 3 hr. The warm reaction mixture was poured into water/ice (10 l). A beige precipitate was collected by filtration and washed with water (2 l). The resulting solid was taken up in DCM (51) and filtered. The filtrate was concentrated in vacuo to give a solid, which was triturated with isopropanol (700 ml), filtered and dried under vacuum to afford the desired product (70.24 g) as a beige solid. (M+H)+=350 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.56-3.79 (m, 8 H) 3.83 (s, 3 H) 6.96 (d, J=8.31 Hz, 1 H) 7.77 (dd, J=8.31, 2.27 Hz, 1 H) 8.34-8.42 (m, 2 H) 8.47 (d, J=2.27 Hz, 1 H).

Provenance & Evidence