Toluene → tert-butyl 1-phenyl-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxylate

HRID 2383430Notes

Reaction equation

HRID 2383430 reaction equation
Br[C:2]1[C:14]2[C:13]3[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=3[CH:7]=[N:6][C:5]=2[NH:4][N:3]=1.C([O-])([O-])=O.[Na+].[Na+].[C:28]1(C)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(O)C.O>[C:28]1([C:2]2[C:14]3[C:13]4[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=4[CH:7]=[N:6][C:5]=3[NH:4][N:3]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 178451611HCID 178451611, compound

Product 1

HCID 178451612tert-butyl 1-phenyl-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxylateYield 52%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of tert-butyl 1-bromo-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxylate (0.540 g, 1.53 mmol) in toluene (8 mL) and ethanol (4 mL) was added phenyl bronic acid (0.371 g, 3.07 mmol) followed by Na2CO3 (0.96 g, 9.18 mmol) as a solution in water (10 mL). The mixture was vortexed and 1,1-Bis(Di-t-butylphosphino)Ferrocene Palladium dichloride (BDtPFPdCl2, CAS#95408-45-0, 0.025 g) was added to the reaction mixture. The reaction was then purged with nitrogen and heated at 90° C. for 16 hours. On completion of the reaction, EtOAc (50 mL) and water (50 mL) was added. The organic layer was separated, washed with brine (2×20 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified using flash column chromatography (SiO2, 50% EtOAc in hexane) to give the pure desired product, tert-butyl 1-phenyl-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridine-7(6H)-carboxylate (0.278 g, 52%) as a white foamy solid. M.p.=>65° C.; 400 MHz 1H NMR (DMSO-d6) δ: 13.72 (s, 1H), 8.38 (s, 1H), 7.73-7.62 (m, 2H), 7.56-7.42 (m, 3H), 4.65 (s, 2H), 3.54-3.45 (m, 2H), 2.88-2.8 (m, 2H), 1.44 (s, 9H); LCMS [M+H]: 351.

Workup

  1. customThe reaction was then purged with nitrogen
  2. customOn completion of the reaction, EtOAc (50 mL) and water (50 mL)
  3. additionwas added
  4. customThe organic layer was separated
  5. washwashed with brine (2×20 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product
  10. customThe crude product was purified

Sources & evidence

ORD record
ord-9fb3837c5572451c8e8394533ccfef35
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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