1-Propanol → HCID 58835261, compound

HRID 1187423Notes

Reaction equation

HRID 1187423 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:23][O:24][CH2:25][CH3:26])[N:14]([CH2:15][CH2:16][CH2:17][O:18][N:19]=[C:20]([CH3:22])[CH3:21])[C:10]=2[C:9]2[N:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)CC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)Cl.O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:23][O:24][CH2:25][CH3:26])[N:14]([CH2:15][CH2:16][CH2:17][O:18][N:19]=[C:20]([CH3:22])[CH3:21])[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:5][C:4]=2[N:3]=1

Participants

9

Reactant 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 58835286HCID 58835286, compound

Product 1

HCID 58835261HCID 58835261, compoundYield 96.7%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

In a pressure vessel under a nitrogen atmosphere, acetone O-{3-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]propyl}oxime (2.50 g, 5.74 mmol), phenylboronic acid (1.05 g, 8.61 nmmol), palladium (II) acetate (13 mg, 0.057 rmmol), triphenylphosphine (45 mg, 0.17 mmol), and 2 M aqueous sodium carbonate (3.45 mL, 6.89 mmol) were combined in 5:1 n-propanol:water (12 mL). The solution was placed under vacuum and back-filled with nitrogen three times. The pressure vessel was sealed and heated at 100° C. for 2 days, then was allowed to cool to ambient temperature. Chloroform (200 mL) was added and the mixture was washed with water (40 mL) and brine (40 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-25% CMA in chloroform) to yield 2.4 g of acetone O-{3-[4-amino-2-(ethoxymethyl)-7-phenyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]propyl}oxime as a yellow powder, mp 134.0-136.0° C.

Workup

  1. additionback-filled with nitrogen three times
  2. customThe pressure vessel was sealed
  3. temperatureto cool to ambient temperature
  4. washthe mixture was washed with water (40 mL) and brine (40 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-25% CMA in chloroform)

Sources & evidence

ORD record
ord-16a4c0aa2f494decaf6c102d2d5143e5
Source dataset
uspto-grants-2014_03
Patent number
US08673932B2

Reaction notes

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