Cesium carbonate → Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

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Reaction Conditions

Reaction Steps

4-Bromo-6-chloro-2-methylpyridazin-3(2H)-one (3.59 g, 16.0 mmol, Eq: 1.00), tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate (4.45 g, 16.0 mmol, Eq: 1.00), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (696 mg, 1.2 mmol, Eq: 0.075) and cesium carbonate (18.3 g, 56.2 mmol, Eq: 3.5) were suspended in dioxane (150 ml) under an argon atmosphere. Finally tris(dibenzylideneacetone)dipalladium(0) (551 mg, 602 μmol, Eq: 0.0375) was added. The reaction mixture was heated at 90° C. overnight. The reaction mixture was filtered over celite, and the celite cake was washed with dioxane several times. The combined filtrate and washes were concentrated in vacuo and the resultant solid was triturated with EtOAc, washed with ether and dried in a vacuum oven overnight at 50° C. to afford 4.57 g of the desired product as a white solid. The combined filtrate and washes were evaporated to dryness and dissolved in CH2Cl2 (4 ml) and the crude material was purified by flash chromatography (silica gel, 120 g Analogix column, 20% to 50% EtOAc in hexanes over 20 min) to afford and additional 582 mg. Total yield (5.15 g, 12.3 mmol, 76.4% yield). (M+H)+=420 m/e; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.50 (s, 9 H) 1.54-1.69 (m, 3 H) 1.83 (d, J=13.64 Hz, 2 H) 2.67 (tt, J=12.38, 3.66 Hz, 1 H) 2.83 (t, J=13.14 Hz, 2 H) 3.82 (s, 3 H) 6.89 (d, J=8.59 Hz, 1 H) 7.51 (dd, J=8.46, 2.40 Hz, 1 H) 8.25 (d, J=2.27 Hz, 1 H) 8.27 (br. s., 1 H) 8.30 (s, 1 H).

Provenance & Evidence