Sodium hydride → tert-butyl 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387567Notes

Reaction equation

HRID 387567 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]2[C:14]3[N:15]=[CH:16][CH:17]=[C:18](O)[C:13]=3[CH:12]=[N:11]2)=[CH:7][CH:6]=1.FC(F)(F)S(N(C1C=CC=CC=1)S(C(F)(F)F)(=O)=O)(=O)=O.[N:43]1([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.[NH4+].[Cl-]>CN(C=O)C>[CH3:3][O:4][C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]2[C:14]3=[N:15][CH:16]=[CH:17][C:18]([N:46]4[CH2:45][CH2:44][N:43]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47]4)=[C:13]3[CH:12]=[N:11]2)=[CH:7][CH:6]=1

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 142176Phenyl triflimideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 178490904HCID 178490904, compound

Product 1

HCID 68758802tert-butyl 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

NaH (0.188 g, 4.70 mmol) in DMF (5 mL) was added dropwise to 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (1.00 g, 3.92 mmol, prepared as described in WO 2007/103308) in DMF (10 mL). The reaction mixture was then warmed to 40° C. and stirred for 30 minutes. After cooling to room temperature, 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.68 g, 4.70 mmol) was added and stirred at room temperature for 1 hour. Then tert-butyl piperazine-1-carboxylate (1.61 g, 8.62 mmol) was added. The mixture was warmed to 80° C. and stirred for 3 hours. The reaction was then cooled to room temperature, and a saturated solution of NH4Cl (30 mL) was added. The mixture was extracted with ethyl acetate (2×30 mL) and dried over sodium sulfate. After removal of solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1) to give tert-butyl 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.64 g, 99% yield) as a solid. MS APCI (+) m/z 424.1 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.24 (s, 1H), 8.13 (d, J=5.2 Hz, 1H), 7.18 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 6.42 (d, J=5.2 Hz, 1H), 5.49 (s, 2H), 3.69 (s, 3H), 3.64 (m, 4H), 3.53 (m, 4H).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringstirred at room temperature for 1 hour
  3. temperatureThe mixture was warmed to 80° C.
  4. stirringstirred for 3 hours
  5. temperatureThe reaction was then cooled to room temperature
  6. extractionThe mixture was extracted with ethyl acetate (2×30 mL)
  7. dry with materialdried over sodium sulfate
  8. customAfter removal of solvent
  9. customthe resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1)

Sources & evidence

ORD record
ord-66cd4dc00e8e4871a24ee89aad5e5713
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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