反应详情

To a solution of 3-{[3-amino-7-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide (for a preparation see Intermediate 14) (22 mg, 0.07 mmol) in anhydrous pyridine (1 mL) and anhydrous dichloromethane (3 mL) (gentle heating of the mixture for a few minutes with a heatgun was required in order for the starting material to go in solution) was added a solution of 5-chloro-2-thiophenesulfonyl chloride (16.71 mg, 0.077 mmol) in anhydrous dichloromethane (0.5 mL). The reaction was stirred at room temperature for 45 min, then at 45° C. for 30 min. A solution of 5-chloro-2-thiophenesulfonyl chloride (16.7 mg) in anhydrous dichloromethane (0.2 mL) was added to the reaction mixture and stirred at 45° C. for 25 h. The reaction mixture was cooled and then partitioned between water and dichloromethane. The organic layer was passed through an hydrophobic frit and evaporated in-vacuo to yield a pale yellow solid. The solid was dissolved in MeOH-DMSO (1 mL) and purified by MDAP on Sunfire C18 column, eluting with solvents A/B (A: 0.1% v/v solution of formic acid in water, B: 0.1% v/v solution of formic acid in acetonitrile). Appropriate fraction was evaporated in-vacuo to yield the title compound as a white solid (15.7 mg, 45%). LCMS (5 min run) RT=2.62 min, ES+ve m/z 495/497 (M+H)+.

1. waitat 45° C. for 30 min
2. stirringstirred at 45° C. for 25 h
3. temperatureThe reaction mixture was cooled
4. custompartitioned between water and dichloromethane
5. customevaporated in-vacuo
6. customto yield a pale yellow solid
7. custompurified by MDAP on Sunfire C18 column
8. washeluting with solvents A/B (A: 0.1% v/v solution of formic acid in water, B
9. customAppropriate fraction was evaporated in-vacuo