4-BroMo-1H-indazol-5-carboxylic acid tert-butyl ester

Uses

tert-Butyl 4-Bromo-1H-indazole-5-carboxylate could be prepared as inhibitors of MNK1 and MNK2, which are useful in treating MNK-mediated diseases.

Synthesis

Step 3: Synthesis of tert-butyl 4-bromo-1H-indazole-5-carboxylate [0245] Tert-butyl 2-bromo-4-fluoro-3-formylbenzoate (4.25 g, 14 mmol) was dissolved in DME (25 mL), hydrazine hydrate (15 mL) was added, and the reaction was heated for 1 hr at 90 °C. After completion of the reaction, it was cooled to room temperature and the reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give tert-butyl 4-bromo-1H-indazole-5-carboxylate as a brown solid (4.1 g, 100% yield). LCMS (Method B): retention time (Rx) = 3.63 min, [M + CH3CN + H]+ = 338/340, [M-H] = 295/297.

References

[1] Patent: WO2010/3025, 2010, A1. Location in patent: Page/Page column 63
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 10, p. 4594 - 4604