Sodium Carbonate → 1,2-dimethyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amine

HRID 1920256Notes

Reaction equation

HRID 1920256 reaction equation
Br[C:2]1[N:6]([CH3:7])[C:5]([CH3:8])=[N:4][C:3]=1[C:9]#[N:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl.[NH2:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][C:33]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)CC.O>[CH3:7][N:6]1[C:2]2[C:37]3[CH:36]=[N:35][CH:34]=[CH:33][C:32]=3[N:31]=[C:9]([NH2:10])[C:3]=2[N:4]=[C:5]1[CH3:8]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 23583876(4-Aminopyridin-3-yl)boronic acid hydrochlorideHCID 23583878960254-14-2

Product 1

HCID 235838791,2-dimethyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amineYield 40.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

5-Bromo-1,2-dimethyl-1H-imidazole-4-carbonitrile (2.00 g, 10.0 mmol), palladium (II) acetate (112 mg, 0.499 mmol), triphenylphosphine (393 mg, 1.50 mmol), and water (3.5 mL) were added to a solution of 4-aminopyridin-3-ylboronic acid hydrochloride salt (3.5 g, 0.020 mol), aqueous sodium carbonate (17.5 mL of 2 M), and n-propanol (17.5 mL). The vessel was evacuated and filled with nitrogen three times. The reaction was sealed and heated under a nitrogen atmosphere at 100° C. for two hours and allowed to cool to room temperature. An analysis by high-performance liquid chromatography (HPLC) indicated the presence of starting material, and additional aqueous sodium carbonate (2.5 mL of 2M), palladium (II) acetate (56 mg), triphenylphosphine (197 mg), and 4-aminopyridin-3-ylboronic acid hydrochloride salt (872 mg) were added. The reaction was heated again at reflux for two hours, allowed to cool to room temperature, and further cooled with ice. A precipitate was present and was isolated by filtration and washed with water to provide 865 mg of 1,2-dimethyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amine. The product was purified by column chromatography on silica gel (eluting with 25% to 40% CMA in chloroform) to provide an analytically pure sample, mp 330-335° C.

Workup

  1. customThe vessel was evacuated
  2. additionfilled with nitrogen three times
  3. customThe reaction was sealed
  4. temperatureto cool to room temperature
  5. additionwere added
  6. temperatureThe reaction was heated again
  7. temperatureat reflux for two hours
  8. temperatureto cool to room temperature
  9. temperaturefurther cooled with ice
  10. customwas isolated by filtration
  11. washwashed with water

Sources & evidence

ORD record
ord-1466dafa98364129bf97e033cfb3e9de
Source dataset
uspto-grants-2012_05
Patent number
US08168802B2

Reaction notes

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