Potassium Carbonate → 4-(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-3-formylpyridin-4-yl)-1-methyl-1H-pyrrole-2-carboxamide

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Reaction Steps

In a 100 mL round-bottomed flask, 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-2-carboxamide (61.0 mg, 244 μmol, Eq: 1.10), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-iodonicotinaldehyde (100 mg, 222 μmol, Eq: 1.00) and [1,1′-bis(Diphenylphosphino)ferrocene]dichloro palladium (II) (16.2 mg, 22.2 μmol, Eq: 0.1) were combined with dioxane (667 μl) to give a red solution. Potassium carbonate (61.3 mg, 443 μmol, Eq: 2) in water (66.7 μl) was added and the resultant suspension was heated to 70° C. and stirred for 32 h. The reaction was diluted with ethyl acetate (10 mL), washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 10% to 15% EtOAc in hexanes to give 4-[2-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-3-formyl-pyridin-4-yl]-1-methyl-1H-pyrrole-2-carboxylic acid amide (28 mgs, 28.2%) as an off white solid. 1H NMR (DMSO-d6) δ: 10.06 (s, 1H), 8.72 (d, J=5.3 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 7.91 (d, J=1.8 Hz, 1H), 7.79 (dd, J=13.3, 1.8 Hz, 1H), 7.73 (d, J=5.3 Hz, 1H), 7.69-7.76 (m, 1H), 7.50 (d, J=1.8 Hz, 1H), 7.17 (d, J=2.0 Hz, 1H), 7.12 (br. s., 1H), 3.93 (s, 3H), 1.39 (s, 9H); MS m/e 448.5 (M+H+).

Provenance & Evidence