Sodium Carbonate → Methyl 3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoate

HRID 348825Notes

Reaction equation

HRID 348825 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([C:10]([N:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])=[O:11])[CH:7]=[C:6](Br)[CH:5]=1.[N:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][C:29]=2B(O)O)[CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:13]([N:12]([CH2:16][CH2:17][CH3:18])[C:10]([C:8]1[CH:9]=[C:4]([CH:5]=[C:6]([C:29]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:30]=2[N:21]=[CH:22][CH:23]=[CH:24]3)[CH:7]=1)[C:3]([O:2][CH3:1])=[O:20])=[O:11])[CH2:14][CH3:15]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343808-Quinolineboronic acidHCID 21939662Methyl 3-bromo-5-(dipropylcarbamoyl)benzoate

Product 1

HCID 21086177Methyl 3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoateYield 77.7%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of methyl-3-bromo-5-[(dipropylamino)carbonyl]benzoate (XLVIII, 200 mg, 0.58 mmol), 8-quinolineboronic acid (200.6 mg, 1.2 mmol), sodium carbonate (870 Micro Liter of a 2 M mixture in water, 1.74 mmol) in toluene (6 mL) is degassed under reduced pressure for 15 minutes and purged with argon. Palladium tetrakis(triphenylphosphine) (139 mg, 0.12 mmol) is added and the reaction mixture is degassed under reduced pressure for 15 minutes and purged with argon. The reaction mixture is heated at reflux overnight, cooled to 20–25 degrees C. and diluted with chloroform. The organic phase is separated and washed with water (3×50 mL), and saline, dried over sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (silica, ethyl acetate/hexanes, 1.3/1) gives methyl 3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoate (XLIX, 176 mg), NMR (300 MHz, CDCl3): delta 8.91, 8.42, 8.21, 8.09, 7.95, 7.86, 7.77, 7.64, 3.94, 3.49, 3.34, 1.64, 0.99 and 0.84.

Workup

  1. customis degassed under reduced pressure for 15 minutes
  2. custompurged with argon
  3. customthe reaction mixture is degassed under reduced pressure for 15 minutes
  4. custompurged with argon
  5. temperatureThe reaction mixture is heated
  6. temperatureat reflux overnight
  7. temperaturecooled to 20–25 degrees C
  8. additionand diluted with chloroform
  9. customThe organic phase is separated
  10. washwashed with water (3×50 mL), and saline
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customPurification by flash column chromatography (silica, ethyl acetate/hexanes, 1.3/1)

Sources & evidence

ORD record
ord-1e5d945fb45d4b2398a0c643106866dd
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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