1-Propanol → tert-Butyl {4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}carbamate

HRID 1818239Notes

Reaction equation

HRID 1818239 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:31][O:32][CH2:33][CH3:34])[N:14]([CH2:15][C:16]3[CH:30]=[CH:29][C:19]([CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:18][CH:17]=3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.B1([C:42]2[CH:47]=[CH:46][CH:45]=[N:44][CH:43]=2)OCCCO1.C(O)CC.C(=O)([O-])[O-].[Na+].[Na+]>C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:31][O:32][CH2:33][CH3:34])[N:14]([CH2:15][C:16]3[CH:30]=[CH:29][C:19]([CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:18][CH:17]=3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:42]3[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=3)=[CH:5][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridineHCID 86593768Tert-butyl [4-(4-amino-7-bromo-2-ethoxymethyl-1h-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamate

Product 1

HCID 86593769tert-Butyl {4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}carbamateYield 64.1%

Reagents, catalysts & solvents 2

HCID 11776TriphenylphosphineCatalystHCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

tert-Butyl [4-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl) benzyl]carbamate (1.15 g, 2.1 mmol), triphenylphosphine (0.005 g), pyridine-3-boronic acid 1,3-propanediol cyclic ester (0.365 g, 2.2 mmol), and n-propanol (3.67 mL) were combined. Aqueous sodium carbonate (2M, 1.12 mL) and water (0.6 mL) were added to the mixture and the flask was flushed with nitrogen. Palladium(II) acetate (0.0013 g) in toluene (0.200 mL) was added, and the flask was again flushed with nitrogen. The flask was sealed and heated in an oil bath at a temperature of 105° C. for 16 hours. The reaction was allowed to cool to room temperature and the mixture was diluted with dichloromethane and water. The layers were separated and the aqueous fraction was extracted with dichloromethane. The organic fractions were combined, washed sequentially with water and saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography eluting with a gradient of CMA/chloroform and subsequent recrystallization from acetonitrile yielded 0.725 g of tert-butyl {4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}carbamate as flocculent white crystals, m.p. 195.5-197.0° C.

Workup

  1. customthe flask was flushed with nitrogen
  2. additionPalladium(II) acetate (0.0013 g) in toluene (0.200 mL) was added
  3. customthe flask was again flushed with nitrogen
  4. customThe flask was sealed
  5. temperatureto cool to room temperature
  6. additionthe mixture was diluted with dichloromethane and water
  7. customThe layers were separated
  8. extractionthe aqueous fraction was extracted with dichloromethane
  9. washwashed sequentially with water and saturated aqueous sodium chloride
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customPurification of the residue by flash column chromatography
  14. washeluting with a gradient of CMA/chloroform and subsequent recrystallization from acetonitrile

Sources & evidence

ORD record
ord-37489dd220bb40f4afe2231e5f1f879a
Source dataset
uspto-grants-2009_10
Patent number
US07598382B2

Reaction notes

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