Hydrochloric Acid → 1-[(4-fluorophenyl)methyl]-N-hydroxy-N-methyl-pyrazolo[3,4-c]pyridine-5-carboxamide

To a stirring solution of methyl 1H-pyrazolo[3,4-c]pyridine-5-carboxylate (100 mg, 0.351 mmol) in methanol (4 mL) was added a 3.0 M solution of LiOH in water (0.351 mL, 1.05 mmol) and the mixture was stirred overnight, then 1.0 M hydrochloric acid in diethyl ether was added (1.05 mL, 1.05 mmol) and the solvent was evaporated under reduced pressure. The crude solid was dissolved in DMF and N-methylhydroxylamine hydrochloride (58 mg, 0.698 mmol) was added followed by triethylamine (214 mL, 1.154 mmol) and HATU (266 mg, 0.698 mmol). The mixture was stirred overnight. Water was added and the mixture was extracted with dichloromethane (3×20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The crude solid was dissolved in DMSO and purified by reverse phase preparative HPLC to provide a white solid (105 mg, 100% yield). 1H NMR (DMSO-d6): & 10.24 (bs, 1H), 9.26 (s, 1H), 8.07 (s, 1H), 7.37 (m, 2H), 7.15 (m, 2H), 5.81 (s, 2H), 3.31 (s, 3H). Anal. HPLC: >95% (@ 254, 222 nM). HRMS calcd for C15H13FN4O2 (M+H) 301.1088, found 301.1096.

1. customthe solvent was evaporated under reduced pressure
2. dissolutionThe crude solid was dissolved in DMF
3. stirringThe mixture was stirred overnight
4. extractionthe mixture was extracted with dichloromethane (3×20 mL)
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe crude solid was dissolved in DMSO
9. custompurified by reverse phase preparative HPLC

ORD record

ord-6166b0edfa184ecca3bd6dfd6bcccd09

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468375B2