Lithium Hydroxide → tert-butyl 4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387579Notes

Reaction equation

HRID 387579 reaction equation
C(O)(C(F)(F)F)=O.COC1C=CC(C[N:15]2[C:19]3=[N:20][CH:21]=[C:22]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[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.CCOCC>[C:37]1([C:22]2[C:23]([N:24]3[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:28][CH2:29]3)=[C:18]3[CH:17]=[N:16][NH:15][C:19]3=[N:20][CH:21]=2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acid2×HCID 90495Di-tert-butyl dicarbonateHCID 68764155tert-butyl 4-(1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 68758199tert-butyl 4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateYield 85.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

TFA (3 mL) was added to tert-butyl 4-(1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.7 g, 3.40 mmol, see Example 1) in DCM (10 mL) and stirred at room temperature for 2 hours. The reaction was concentrated to dryness and dried under vacuum for 3 hours. TFA (13.1 mL, 170 mmol) was then added, and the mixture was heated at 65° C. for 1 hour. The reaction was then concentrated to dryness. The resulting residue was added to THF (10 mL), an aqueous LiOH solution (6.81 mL, 2M) and Boc2O (2.23 g, 10.2 mmol) and stirred at room temperature for 3 days. Ether (50 mL) was then added. The organic layer was separated, washed with brine, and dried over sodium sulfate. After removal of the solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1) to give tert-butyl 4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.1 g, 85%) as a solid. MS APCI (+) m/z 380.1 detected.

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. customdried under vacuum for 3 hours
  3. temperaturethe mixture was heated at 65° C. for 1 hour
  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 the solvent
  10. customthe resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-3f7585ed2fe44c0abeb3313cbcc2aba8
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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