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With sodium carbonate;dichloro-1,1'-bis(diphosphino)ferrocene-palladium(II); In 1,4-dioxane; water; at 100℃; for 20h; |
Example 67; JV-[2-Chloro-5-(4-oxo- 1 ,4-dihydro-6-quinazolinyl)-3-pyridinyl]benzenesulfonamidea) lambda/-[2-chloro-5-(6-quinazolinyl)-3-pyridinyl]benzenesulfonamide; A slurry of N-(5-bromo-2-chloro-3-pyridinyl)benzenesulfonamide (493 mg, 1.418 mmol), bis(pinacolato)diboron (375 mg, 1.477 mmol), potassium acetate (232 mg, 2.363 mmol) and PdCl2(dppf)-CH2Cl2 (48.2 mg, 0.059 mmol) in anhydrous 1,4- dioxane (9.60 mL) was heated at 100 0C for 6 h. The reaction was cooled slightly then treated with <strong>[89892-21-7]6-bromoquinazoline</strong> (247 mg, 1.182 mmol), 2 M aqueous sodium carbonate (2.363 mL, 4.73 mmol) and another portion of PdCl2(dppf)-CH2Cl2 (48.2 mg, 0.059 mmol) then heated at 100 0C for a further 20 h. The reaction was cooled to room temperature then concentrated under reduced pressure. The resulting crude residue was slurried in ethyl acetate then treated with decolorizing charcoal and <n="81"/>anhydrous sodium sulfate. Filtered through a short pad of silica then the filtrate was evaporated under reduced pressure. The residue was purified by silica gel chromatography with 40% hexanes in ethyl acetate. The combined, desired fractions were evaporated to give the product (236 mg, 49.8%) as a white solid. MS(ES)+ m/e 396.7 [M+H]+. IH NMR (400 MHz, DMSO-J6) delta ppm 7.60 (t, J=7.58 Hz, 3 H) 7.66 - 7.74 (m, 1 H) 7.78 (d, J=7.07 Hz, 2 H) 7.77 (s, 1 H) 8.12 - 8.21 (m, 3 H) 8.34 (dd, J=8.84, 2.27 Hz, 1 H) 8.51 (d, J=2.02 Hz, 1 H) 8.76 (d, J=2.27 Hz, 1 H) 9.36 (s, 1 H) 9.70 (s, 1 H) 10.54 (s, 1 H). |