反应详情

A mixture of 4-(5-amino-6-methylisoquinolin-1-ylamino)benzonitrile (0.250 g, 0.91 mmol) and 9-(4-methoxybenzyl)-6-(2-fluoropyridin-3-yl)-9H-purine (0.34 g, 1.0 mmol) in anhydrous THF (20 mL) was treated dropwise with lithium bis(trimethylsilyl)amide (1.0 M solution in THF; 2.7 mlL, 2.7 mmol) to give a dark suspension. The suspension was sonicated for 2 min and then stirred at RT for 30 min. The reaction mixture was sonicated again for 2 min. The mixture was treated with 1N aq HCl (5 mL) and stirred at RT for 10 min. The reaction mixture was added to satd NaHCO3 (70 mL) and extracted with 3:1 CHCl3:IPA (3×50 mL). The combined organic layers were washed with satd NaCl, dried over Na2SO4, filtered, and concentrated in vacuo to give 840 mg crude product. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (80 g), eluting with a gradient of 10% to 50% EtOAc in CH2Cl2, to give 4-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile. MS (ESI, pos. ion) m/z: 590.2 [M+H]+

1. customto give a dark suspension
2. customThe suspension was sonicated for 2 min
3. customThe reaction mixture was sonicated again for 2 min
4. stirringstirred at RT for 10 min
5. extractionextracted with 3:1 CHCl3
6. washThe combined organic layers were washed with satd NaCl
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give 840 mg crude product
11. customchromatographed through a Redi-Sep® pre-packed silica gel column (80 g)
12. washeluting with a gradient of 10% to 50% EtOAc in CH2Cl2