Potassium tert-butoxide → 6-{[5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-(5-methylpyrazin-2-yl)quinazoline-4-amine

HRID 1517283Notes

Reaction equation

HRID 1517283 reaction equation
[CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10](F)=[N:11][CH:12]=1)[CH3:2].CC(C)([O-])C.[K+].[CH3:23][C:24]1[N:25]=[CH:26][C:27]([NH:30][C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([OH:41])[CH:39]=3)[N:34]=[CH:33][N:32]=2)=[N:28][CH:29]=1>CS(C)=O>[CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([O:41][C:38]2[CH:39]=[C:40]3[C:35](=[CH:36][CH:37]=2)[N:34]=[CH:33][N:32]=[C:31]3[NH:30][C:27]2[CH:26]=[N:25][C:24]([CH3:23])=[CH:29][N:28]=2)=[N:11][CH:12]=1)[CH3:2]

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 684297065-(2,2-Diethoxyethoxy)-2-fluoropyridineHCID 1356182224-((5-Methylpyrazin-2-yl)amino)quinazolin-6-ol

Product 1

HCID 684290706-{[5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-(5-methylpyrazin-2-yl)quinazoline-4-amineYield 80.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

5-(2,2-Diethoxyethoxy)-2-fluoropyridine (680 mg, 3.0 mmol) and potassium tert-butoxide (670 mg, 5.9 mmol) were added to a dimethyl sulfoxide solution (10 ml) of 4-[(5-methylpyrazin-2-yl)amino]quinazolin-6-ol (500 mg, 1.97 mmol), and stirred under a nitrogen atmosphere at 130° C. for 24 hours. The reaction solution was cooled to room temperature, and extracted with a mixed solution of chloroform/methanol (9:1). The organic layer was washed with aqueous saturated ammonium chloride solution and saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=95:5) to obtain 6-{[5-(2,2-diethoxyethoxy)pyridin-2-yl]oxy}-N-(5-methylpyrazin-2-yl)quinazoline-4-amine (730 mg, yield: 80%) as a yellow solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with a mixed solution of chloroform/methanol (9:1)
  3. washThe organic layer was washed with aqueous saturated ammonium chloride solution and saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (chloroform:methanol=95:5)

Sources & evidence

ORD record
ord-7a0944affe964f629f2be8f8efc40b9e
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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