Water → HCID 10406233, compound

HRID 1373953Notes

Reaction equation

HRID 1373953 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:15]([NH:16][CH:17]([CH3:19])[CH3:18])[C:14]([CH2:20][CH2:21][CH3:22])=[N:13][C:7]=3[C:8]([NH2:12])=[N:9][C:10]=2[CH:11]=1.B1([C:29]2[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=2)OCCCO1.C(=O)([O-])[O-].[Na+].[Na+].O>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>[CH:17]([NH:16][N:15]1[C:6]2[C:5]3[CH:4]=[CH:3][C:2]([C:29]4[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=4)=[CH:11][C:10]=3[N:9]=[C:8]([NH2:12])[C:7]=2[N:13]=[C:14]1[CH2:20][CH2:21][CH3:22])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridineHCID 69177518HCID 69177518, compound

Product 1

HCID 10406233HCID 10406233, compoundYield 51.8%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 7-bromo-N1-isopropyl-2-propyl-1H-imidazo[4,5-c]quinoline-1,4-diamine (1.00 g, 2.76 mmol) in 20 mL of 1-propanol was treated with pyridine-3-boronic acid 1,3-propane diol cyclic ester (0.540 g, 3.31 mmol). The head-space of the reaction flask was purged and back-filled with nitrogen (3×). The reaction mixture was then treated with triphenylphosphine (11 mg, 0.041 mmol), sodium carbonate (1.66 mL, 3.31 mmol, 2 M solution in water), water (2 mL) and palladium(II) acetate (3.1 mg, 0.014 mmol). Again the head-space of the reaction flask was purged and back-filled with nitrogen (3×). The reaction was heated to 100° C. After 17 h, the reaction was cooled to ambient temperature and concentrated under reduced pressure to yield a brown solid. The solid was dissolved and partitioned between 15 mL of water and 15 mL of chloroform and then separated. The aqueous portion was extracted with chloroform (2×15 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a tan solid. The solid was purified by chromatography (SiO2, 95:5 CHCl3:MeOH) and recrystallized from acetonitrile to give 0.515 g of N1-isopropyl-2-propyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinoline-1,4-diamine as white crystals.

Workup

  1. customThe head-space of the reaction flask was purged
  2. additionback-filled with nitrogen (3×)
  3. customAgain the head-space of the reaction flask was purged
  4. additionback-filled with nitrogen (3×)
  5. temperaturethe reaction was cooled to ambient temperature
  6. concentrationconcentrated under reduced pressure
  7. customto yield a brown solid
  8. dissolutionThe solid was dissolved
  9. custompartitioned between 15 mL of water and 15 mL of chloroform
  10. customseparated
  11. extractionThe aqueous portion was extracted with chloroform (2×15 mL)
  12. washThe combined organic extracts were washed with brine (15 mL)
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customto yield a tan solid
  17. customThe solid was purified by chromatography (SiO2, 95:5 CHCl3:MeOH)
  18. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-0e0ff6e3a659439789d1932e77a2366c
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

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