反应详情

温度

65 °C

A mixture of 5-chloro-N-[(5-chloro-2-thienyl)sulfonyl]-N-[4-(methyloxy)-1H-indazol-3-yl]-2-thiophenesulfonamide (for a preparation see Intermediate 10) (150 mg, 0.28 mmol), (3-{[2-(dimethylamino)ethyl]oxy}phenyl)methanol (73 mg, 0.37 mmol), triphenylphosphine (113 mg, 0.43 mmol) and di-tert-butyl azodicarboxylate (132 mg, 0.57 mmol) in THF (15 mL) was heated to 65° C., O/N. The mixture was evaporated under reduced pressure, the residue was dissolved in MeOH, and then loaded on a SCX-2 ion-exchange cartridge (20 g) and eluted with sequential solvents methanol, 2M ammonia in methanol. The appropriate fractions were combined and evaporated in vacuo to give the crude product. This was dissolved in DCM and purified by chromatography on silica (20 g cartridge) on Flashmaster using a 0-15% methanol (containing 1% Et3N)-dichloromethane over 20 min. The appropriate fraction was evaporated in vacuo to give the title product (140 mg, 70%) as a white foam. LCMS (System F) RT=1.27 min, ES+ve m/z 701/703 (M+H)+.

1. customThe mixture was evaporated under reduced pressure
2. dissolutionthe residue was dissolved in MeOH
3. washeluted with sequential solvents methanol, 2M ammonia in methanol
4. customevaporated in vacuo
5. customto give the crude product
6. custompurified by chromatography on silica (20 g cartridge) on Flashmaster
7. customover 20 min
8. customThe appropriate fraction was evaporated in vacuo