Hydrazine → (S)-3-(6-(3-isobutylpiperazin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-tert-butyl 4-(6-(2-fluoronicotinoyl)pyrazin-2-yl)-2-isobutylpiperazine-1-carboxylate (160 mg, 0.3608 mmol) in THF (3 mL) was added hydrazine (1M in THF) (360.8 μL of 1 M, 0.3608 mmol) and the solution heated to 75° C. for 2 hrs. The reaction was allowed to cool and concentrated to give a yellow solid. This was columned on silica gel eluting with 1:1 EtOAc/hexanes to give (S)-3-(6-(3-isobutylpiperazin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine as a pale yellow solid. The Boc intermediate was dissolved in DCM (6 mL) and TFA (3 mL, 38.94 mmol) was added and the solution stirred at rt for 1 hr. Reaction was concentrated and partitioned between EtOAc and Sat. Na2CO3 and the organic washed with brine, dried (MgSO4) and concentrated to give a yellow solid. It was columned on silica gel eluting with 10% MeOH in DCM (1% NH4OH) to give (S)-3-(6-(3-isobutylpiperazin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine as an off white solid (52 mg, 42% 2 steps). ES+ 338. 1HNMR (DMSO) 0.92-0.94 (6H, dd), 1.24-1.35 (2H, m), 1.79-1.88 (1H, m), 2.56-2.61 (1H, m), 2.67-2.80 (2H, m), 2.92-3.05 (2H, m), 4.25 (1H, d), 4.33 (1H, d), 7.32 (1H, dd), 8.30 (1H, s), 8.57-8.61 (2H, m), 8.73 (1H, d), 14.14 (1H, brs).

Provenance & Evidence