反应详情

4-(Methyloxy)-1H-indazol-3-amine (for a preparation see Intermediate 1) (490 mg, 3 mmol) and potassium hydroxide (185 mg, 3.30 mmol) were dissolved in DMSO (30 mL). The reaction was left to stir for 30 min, before 4-(bromomethyl)-2-fluoro-1-(methyloxy)benzene (657 mg, 3.00 mmol) was added to the reaction mixture and stirred for 1 h at room temperature under nitrogen. The reaction mixture was diluted with ethyl acetate (250 mL) and washed with water (2×250 mL) and brine (250 mL). The organic layer was dried over anhydrous magnesium sulphate and filtered before being evaporated in vacuo to afford a brown oil. The residue was loaded in dichloromethane on a silica 100 g cartridge and purified by chromatography on Flashmaster using a 0-100% ethyl acetate-dichloromethane over 40 min. The appropriate fractions were combined and evaporated in vacuo and the residue re-purified by chromatography on silica 70 g using a 0-50% ethyl acetate-dichloromethane over 40 min. The appropriate fractions were combined and evaporated in vacuo to give the title compound (432 mg, 48%) as an off-white solid. LCMS (System A) RT=0.96 min, ES+ve m/z 302 (M+H)+.

1. waitThe reaction was left
2. additionwas added to the reaction mixture
3. washwashed with water (2×250 mL) and brine (250 mL)
4. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
5. filtrationfiltered
6. custombefore being evaporated in vacuo
7. customto afford a brown oil
8. custompurified by chromatography on Flashmaster
9. customover 40 min
10. customevaporated in vacuo
11. customthe residue re-purified by chromatography on silica 70 g
12. customover 40 min
13. customevaporated in vacuo