Potassium Hydroxide → 4-{[3-Amino-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide

To a solution of 4-(methyloxy)-1H-indazol-3-amine (for a preparation see Intermediate 1) (0.816 g, 5 mmol) in DMSO (50 mL) at room temperature under nitrogen was added potassium hydroxide (0.561 g, 10.0 mmol). After stirring the resulting deep red solution for 25 min 4-(chloromethyl)benzamide (0.848 g, 5.00 mmol) was added in one portion. The reaction mixture was stirred for a further 30 min and then poured into water (250 mL), forming an emulsion. The reaction mixture was extracted using chloroform (3×250 mL). The combined organic solutions were washed with water (250 mL) and passed through hydrophobic frit. The solvent was removed in vacuo and the residue was loaded in dichloromethane to a silica (100 g) cartridge and purified by chromatography on Flashmaster eluting with 0-100% ethyl acetate-cyclohexane+0-20% methanol-ethyl acetate over 60 min. The appropriate fractions were combined and evaporated in vacuo to give the title compound (1.18 g, 80%). LCMS: (System A) RT=0.69 min, ES+ve m/z 297 (M+H)+.

1. customat room temperature
2. additionwas added in one portion
3. customforming an emulsion
4. extractionThe reaction mixture was extracted
5. washThe combined organic solutions were washed with water (250 mL)
6. customThe solvent was removed in vacuo
7. custompurified by chromatography on Flashmaster
8. washeluting with 0-100% ethyl acetate-cyclohexane+0-20% methanol-ethyl acetate over 60 min
9. customevaporated in vacuo

ORD record

ord-a16f704e027248808cd6d67c03378fe5

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08357716B2