反应详情

温度

80 °C

1-[({5-[6-Bromo-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)amino]-3-(4-morpholinyl)-2-propanol (100 mg, 0.346 mmol), N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (81 mg, 0.247 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (25.35 mg, 0.0345 mmol) and potassium phosphate tribasic (110.5 mg, 0.5195 mmol) were added to a mixture of 1,4-dioxane (2.5 ml) and water (0.25 ml). The reaction mixture was heated under microwave irradiation at 80° C. for 30 mins and then 100° C. for 10 mins. The mixture was then passed through a 1 g silica SPE cartridge, washing with MeOH. The solvent was removed under a stream of nitrogen and the residue was partitioned between DCM (10 ml) and water (10 ml), separated by a hydrophobic frit and the solvent again removed under a stream of nitrogen. The protected compound was dissolved in 1,4-dioxane (1 ml) and sodium hydroxide (1 ml) and stirred at room temperature for 1 h. The mixture was neutralised with addition of 2M HCl, dissolved in DMSO, filtered through a filter tube and purified by high pH MDAP (Method E). The appropriate fractions and waste were evaporated to dryness in vacuo. The residue was dissolved in 1:1 DMSO/water and purified by preparative HPLC using the following method:

1. washwashing with MeOH
2. customThe solvent was removed under a stream of nitrogen
3. customthe residue was partitioned between DCM (10 ml) and water (10 ml)
4. customseparated by a hydrophobic frit
5. customthe solvent again removed under a stream of nitrogen
6. dissolutionThe protected compound was dissolved in 1,4-dioxane (1 ml)
7. additionThe mixture was neutralised with addition of 2M HCl
8. dissolutiondissolved in DMSO
9. filtrationfiltered through a filter tube
10. custompurified by high pH MDAP (Method E)
11. customThe appropriate fractions and waste were evaporated to dryness in vacuo
12. dissolutionThe residue was dissolved in 1:1 DMSO/water
13. custompurified by preparative HPLC