Sodium Carbonate → HCID 57576711, compound

HRID 599440Notes

Reaction equation

HRID 599440 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:19][O:20][N:21]=[C:22]([CH3:24])[CH3:23])[N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:19][O:20][N:21]=[C:22]([CH3:24])[CH3:23])[N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:5][C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 57576748HCID 57576748, compound

Product 1

HCID 57576711HCID 57576711, compoundYield 43.5%

Reagents, catalysts & solvents 2

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

A flask containing mixture of acetone O-{[4-amino-7-bromo-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]methyl}oxime (prepared as described in Example 96, 1.16 g, 2.86 mmol), phenylboronic acid (0.42 g, 3.43 mmol), triphenylphosphine (7 mg, 0.026 mmol), 2 M aqueous sodium carbonate (4.3 mL, 8.58 mmol), and 5:1 propanol/water (18 mL) was evacuated under reduced pressure and back-filled with nitrogen gas. Palladium(II) acetate (2 mg, 0.009 mmol) was added, and the flask was again evacuated and back-filled with nitrogen gas. The reaction mixture was heated at 100° C. for 18 hours. The reaction mixture was allowed to cool to room temperature and was diluted with dichloromethane (40 mL) and water (30 mL). The aqueous layer was extracted with dichloromethane (2×15 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated to afford a tan solid. The solid was purified by chromatography using a HORIZON HPFC system (silica gel, gradient elution with 0-30% CMA in chloroform) to afford a thick oil that was crystallized from acetonitrile. The crystals were isolated by filtration and dried at 80° C. in a vacuum oven to yield 0.501 g of acetone O-{[4-amino-1-(2-methylpropyl)-7-phenyl-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]methyl}oxime as a white powder, mp 196-197° C.

Workup

  1. additionA flask containing
  2. custom1 propanol/water (18 mL) was evacuated under reduced pressure
  3. additionback-filled with nitrogen gas
  4. customthe flask was again evacuated
  5. additionback-filled with nitrogen gas
  6. temperatureto cool to room temperature
  7. additionwas diluted with dichloromethane (40 mL) and water (30 mL)
  8. extractionThe aqueous layer was extracted with dichloromethane (2×15 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a tan solid
  13. customThe solid was purified by chromatography
  14. washa HORIZON HPFC system (silica gel, gradient elution with 0-30% CMA in chloroform)
  15. customto afford a thick oil that
  16. customwas crystallized from acetonitrile
  17. customThe crystals were isolated by filtration
  18. customdried at 80° C. in a vacuum oven

Sources & evidence

ORD record
ord-ff4e3a4faa5148a795c235d8e4180398
Source dataset
uspto-grants-2011_03
Patent number
US07897767B2

Reaction notes

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