82% |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium 2-ethylhexanoic acid; In 1,4-dioxane; at 110℃; for 4.0h;Inert atmosphere; |
To a solution of 5-bromo-1-methyl-1H-benzo[dlimmdazole (1.0 g, 4.74 mmol) indioxane (10 mL) were added 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane) (1.5 g,5.68 mmol), sodium 2-ethylhexanoate (1.968 g, 11.86 mmol) and Pd(dppf)C12.DCM (247 mg,0.474 mmol) under N2. The mixture was stirred at 110 C for 4 h, poured into H20 (60 mL) andextracted with EA (50 mL x 2). The organic layers were dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and purified by silica gel column chromatography (PE/EA = 1/1) to afford 1 -methyl-S -(4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H-benzo[d]imidazole (1.0 g, 82 %) as a yellow solid. LC-MS m/z: 259.1 [M+Hf?. tR= 1.67 min. |
49% |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 80℃; for 16.0h;Inert atmosphere; |
To a solution of <strong>[53484-15-4]5-bromo-1-methyl-1H-benzo[d]imidazole</strong> (200 mg, 0.33 mmol, 1 eq.) in 1,4-dioxane (10 mL) was added 5-(4,4,5,5-bis(pinacolato)diboron (287 mg, 1.13 mmol, 1.2 eq.), KOAc (276 mg, 2.82 mmol, 2 eq.), PdCl2(dppf).DCM (76 mg, 0.09 mmol, 0.09 eq.). The reaction mixture was deoxygenated with N2 and the reaction mixture was stirred at 80 C. for 16 h. The reaction was monitored by LCMS and found to be complete after 18 h. The reaction mixture was cooled to RT, diluted with water (50 mL) and extracted with ethyl acetate (2*50 mL). Combined organic layer was washed with brine (20 mL) and dried over sodium sulfate. Removal of solvent under reduced pressure gave crude which was purified by Combi-Flash (0-100% EtOAC-Hexane) to afford the desired product (120 mg, 49%) as brown oil. |
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With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 160℃; for 0.333333h;Inert atmosphere; Microwave irradiation; |
To a mixture of <strong>[53484-15-4]5-bromo-1-methyl-1H-benzimidazole</strong> obtained in Reference Example 18 (1.0 g), Pin2B2 (1.8 g), PdCl2(dppf).CH2Cl2 (311 mg), and potassium: acetate (2.3 g) was added 1,4-dioxane (10 mL), the interior of the vessel was purged with argon, and the mixture was reacted under microwave irradiation (Biotage INITIATOR, at 160 C. for 20 minutes). The reaction mixture was filtered, through Celite, and the filtrate was concentrated under reduced pressure. To the resulting residue were successively added PdCl2(dppf).CH2Cl2 (194 mg), 2,6-dichloro-4-cyclopropylpyridine obtained in Reference Example 2 (900 mg), potassium carbonate (2.0 g) and 1,4-dioxane-water (3:1, 25 mL), and the interior of the vessel was purged with argon. The reaction mixture was stirred at 100 C. for 1.5 hours, and filtered through Celite, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography to give 560 mg of the title compound as a pale yellow solid. |