Diethyl Ether → HCID 178476653, compound

HRID 2359893Notes

Reaction equation

HRID 2359893 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][N:14]([CH2:20][C:21]3[C:26]([O:27][CH3:28])=[CH:25][CH:24]=[CH:23][C:22]=3[O:29][CH3:30])[C:15]([NH2:19])=[N:16]2)=[CH:11][CH:10]=1.C([O:33]CC)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:26]([O-:27])(=[O:33])[CH3:21].[NH:1]([C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][N:14]([CH2:20][C:21]3[C:22]([O:29][CH3:30])=[CH:23][CH:24]=[CH:25][C:26]=3[O:27][CH3:28])[C:15]([NH3+:19])=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 6115AnilineHCID 68546471HCID 68546471, compound

Product 1

HCID 178476653HCID 178476653, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Procedure

A three-necked flask was heated under argon and then charged with sodium tert-butylate (0.178 g, 1.99 mol), (R/S)-1,1′-binaphthaline-2,2′-diylphosphate (0.092 g, 0.15 mmol) and tris(dibenzylidene acetone)dipalladium (0) (0.121 g, 0.13 mmol) under a protective atmosphere and suspended in 10 mL toluene. Aniline (0.25 mL, 2.79 mmol) and 7-bromo-3-(2,6-dimethoxybenzyl)-3,4-dihydroquinazolin-2-amine (0.500 g, 1.33 mmol), suspended in 20 mL toluene, were then added one after the other to the starting reagents. The reaction mixture was heated at reflux for 3 hours. The reaction was not yet complete, so that first the mixture had to heated at room temperature for 12 hours and then for 5 hours at reflux. After the reaction was concluded, the mixture was cooled to room temperature, diluted with diethyl ether and the resulting solids were filtered out. For purification, the solids were dissolved in acetonitrile/water (1:1) and acetic acid and purified by preparative HPLC (Merck, Chromolith RP18) with the eluents acetonitrile and water (0.1M % acetic acid) with a gradient of 20% to 50% acetonitrile in 30 minutes. After freeze drying, the desired product was isolated via the lyophilizer. Yield: 50 mg (0.129 mmol, 10%).

Workup

  1. temperatureA three-necked flask was heated under argon
  2. additionwere then added one after the other to the starting reagents
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 3 hours
  5. temperaturefor 5 hours at reflux
  6. temperaturethe mixture was cooled to room temperature
  7. filtrationthe resulting solids were filtered out
  8. customFor purification
  9. dissolutionthe solids were dissolved in acetonitrile/water (1:1)
  10. customacetic acid and purified by preparative HPLC (Merck, Chromolith RP18) with the eluents acetonitrile and water (0.1M % acetic acid) with a gradient of 20% to 50% acetonitrile in 30 minutes
  11. customAfter freeze drying

Sources & evidence

ORD record
ord-77e844b2345d41deafc116ba69818ee1
Source dataset
uspto-grants-2014_04
Patent number
US08686002B2

Reaction notes

Loading…