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

HRID 717585Notes

Reaction equation

HRID 717585 reaction equation
F[C:2]1[N:32]=[CH:31][CH:30]=[CH:29][C:3]=1[C:4]([C:6]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[C@@H:14]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:13]2)[CH:9]=[N:8][CH:7]=1)=O.[NH2:33][NH2:34]>C1COCC1>[CH2:25]([C@@H:14]1[NH:15][CH2:16][CH2:17][N:12]([C:10]2[N:11]=[C:6]([C:4]3[C:3]4[C:2](=[N:32][CH:31]=[CH:30][CH:29]=4)[NH:34][N:33]=3)[CH:7]=[N:8][CH:9]=2)[CH2:13]1)[CH:26]([CH3:27])[CH3:28]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 67608074(S)-tert-butyl 4-(6-(2-fluoronicotinoyl)pyrazin-2-yl)-2-isobutylpiperazine-1-carboxylate

Product 1

HCID 178445829(S)-3-(6-(3-isobutylpiperazin-1-yl)pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

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).

Workup

  1. temperatureto cool
  2. concentrationconcentrated
  3. customto give a yellow solid

Sources & evidence

ORD record
ord-9fe38dcb684f48d3b9f2b0feb1e1c9a0
Source dataset
uspto-grants-2015_11
Patent number
US09193722B2

Reaction notes

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