Lithium Hydroxide → tert-butyl 4-(1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387568Notes

Reaction equation

HRID 387568 reaction equation
C(O)(C(F)(F)F)=O.COC1C=CC(C[N:15]2[C:19]3=[N:20][CH:21]=[CH:22][C:23]([N:24]4[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]4)=[C:18]3[CH:17]=[N:16]2)=CC=1.[Li+].[OH-].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C(Cl)Cl.O.CCOCC>[NH:15]1[C:19]2=[N:20][CH:21]=[CH:22][C:23]([N:24]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]3)=[C:18]2[CH:17]=[N:16]1

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acid2×HCID 90495Di-tert-butyl dicarbonateHCID 68758802tert-butyl 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 68760612tert-butyl 4-(1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateYield 48.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

TFA (6 mL) was added to tert-butyl 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.59 g, 3.754 mmol) in DCM (30 mL) and stirred at room temperature for 1 hour. The reaction was then concentrated to dryness and dried under vacuum for 3 hours. TFA (8.68 mL, 112.6 mmol) was added, and the mixture was heated at 65° C. for 2 hours. The reaction was then concentrated to dryness. The resulting residue was added to THF (10 mL), a LiOH solution (3.8 mL, 7.5 mmol, 2N) and Boc2O (0.98 g, 4.50 mmol) and stirred at room temperature for 1 hour. Ether (20 mL) and water (10 mL) were then added. The organic layer was separated, washed with brine, and dried over sodium sulfate. After removal of solvent, the resulting residue was purified by chromatography (hexane:ethyl acetate, 3:1) to give tert-butyl 4-(1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.55 g, 48%) as a solid. MS APCI (+) m/z 304.1 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.21 (s, 1H), 8.08 (d, J=5.6 Hz, 1H), 6.37 (d, J=5.6 Hz, 1H), 3.60 (m, 4H), 3.54 (m, 4H), 2.50 (s, 9H).

Workup

  1. concentrationThe reaction was then concentrated to dryness
  2. customdried under vacuum for 3 hours
  3. temperaturethe mixture was heated at 65° C. for 2 hours
  4. concentrationThe reaction was then concentrated to dryness
  5. additionThe resulting residue was added to THF (10 mL)
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. customAfter removal of solvent
  10. customthe resulting residue was purified by chromatography (hexane:ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-3cbb3c93a7ac49d68293d5310cf050ec
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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