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

HRID 81644

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

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

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

Sources & evidence

ORD record: ord-a31ac465982541f791cd2e29ee0d6eb2
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846700B2

Linked notes

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