Sodium Carbonate → HCID 59130441, compound

HRID 1992608Notes

Reaction equation

HRID 1992608 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:25][CH2:26][CH3:27])[N:14]([CH2:15][CH2:16][CH2:17][O:18][NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[C:29]1(B(O)O)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)CC>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:25][CH2:26][CH3:27])[N:14]([CH2:15][CH2:16][CH2:17][O:18][NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:5][C:4]=2[N:3]=1

Participants

10

Reactant 4

HCID 10340Sodium Carbonate2×HCID 11776Triphenylphosphine3×HCID 66827Phenylboronic Acid3×HCID 59130465HCID 59130465, compound

Product 1

HCID 59130441HCID 59130441, compound

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalyst3×HCID 962WaterSolventHCID 10311-PropanolSolventHCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

Under a nitrogen atmosphere, N-[3-(4-amino-7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propoxy]-2-methylpropanamide (300 mg, 0.67 mmol), phenylboronic acid (123 mg, 1.01 mmol), a solution of palladium (II) acetate (1.5 mg, 0.0067 mmol) in hot toluene (0.2 mL), triphenylphosphine (5.3 mg, 0.02 mmol), and 2 M aqueous sodium carbonate (0.4 mL, 0.8 mmol) were combined in 5:1 n-propanol:water (1.44 mL). The solution was placed under vacuum and back-filled with nitrogen gas three times and then heated at 100° C. for 16 hours. Additional phenylboronic acid (123 mg, 1.01 mmol), palladium (II) acetate (1.5 mg, 0.0067 mmol), and triphenylphosphine (5.3 mg, 0.02 mmol) were added, and the reaction was heated at 100° C. overnight. Again, additional phenylboronic acid (123 mg, 1.01 mmol), palladium (II) acetate (1.5 mg, 0.0067 mmol), and triphenylphosphine (5.3 mg, 0.02 mmol) were added, plus 2 M aqueous sodium carbonate (0.4 mL, 0.8 mmol), and the reaction was heated at 100° C. overnight. After cooling to room temperature, the reaction mixture was diluted with chloroform (60 mL) and washed with water (2×10 mL) and brine (10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% CMA in chloroform) followed by recrystallization from acetonitrile. The final product was isolated and dried under vacuum at 100° C. to yield N-[3-(4-amino-7-phenyl-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propoxy]-2-methylpropanamide as a white powder, mp 169.0-171.0° C.

Workup

  1. additionback-filled with nitrogen gas three times
  2. temperaturethe reaction was heated at 100° C. overnight
  3. temperatureAfter cooling to room temperature
  4. washwashed with water (2×10 mL) and brine (10 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% CMA in chloroform)
  9. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-788b63fe350d4b9e8ccd58b052b8688b
Source dataset
uspto-grants-2010_01
Patent number
US07648997B2

Reaction notes

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