Sodium Carbonate → 1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amine

HRID 1920266Notes

Reaction equation

HRID 1920266 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].I[C:8]1[N:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:11]([CH2:17][CH2:18][CH3:19])=[N:10][C:9]=1[C:20]#[N:21].Cl.[NH2:23][C:24]1[CH:29]=[CH:28][N:27]=[CH:26][C:25]=1B(O)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O.C(O)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:15][CH:14]([CH3:16])[CH2:13][N:12]1[C:8]2[C:29]3[CH:28]=[N:27][CH:26]=[CH:25][C:24]=3[N:23]=[C:20]([NH2:21])[C:9]=2[N:10]=[C:11]1[CH2:17][CH2:18][CH3:19]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 23583876(4-Aminopyridin-3-yl)boronic acid hydrochlorideHCID 585001345-iodo-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile

Product 1

HCID 585001461-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amineYield 37.1%

Reagents, catalysts & solvents 3

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

Procedure

A solution of sodium carbonate (572 mg, 5.4 mmol) in deionized water (6 mL) was added to a solution of 5-iodo-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile (634 mg, 2.0 mmol) and 4-aminopyridin-3-ylboronic acid hydrochloride salt (383 mg, 2.2 mmol) in n-propanol (15 mL), and nitrogen was bubbled through the resultant solution for 15 minutes. Palladium (II) acetate (22 mg, 0.1 mmol) and triphenylphosphine (79 mg, 0.3 mmol) were added. The reaction was evacuated and purged with nitrogen several times and then heated at reflux for 18 hours. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was separated and extracted several times with ethyl acetate. The combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 7% methanol in dichloromethane) to provide 210 mg of 1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amine as a tan solid.

Workup

  1. customwas bubbled through the resultant solution for 15 minutes
  2. customThe reaction was evacuated
  3. custompurged with nitrogen several times
  4. temperatureheated
  5. temperatureat reflux for 18 hours
  6. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate
  7. customThe aqueous layer was separated
  8. extractionextracted several times with ethyl acetate
  9. washThe combined organic fractions were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude product was purified by column chromatography on silica gel (eluting with 7% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f00245ef8e1f4498bf89285462e0ec33
Source dataset
uspto-grants-2012_05
Patent number
US08168802B2

Reaction notes

Loading…