Dimethylacetamide → 6-{[2-(2,2-diethoxyethoxy)pyrimidin-5-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine

HRID 1517267Notes

Reaction equation

[CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][O:6][C:7]1[N:12]=[CH:11][C:10](F)=[CH:9][N:8]=1)[CH3:2].CC(C)([O-])C.[K+].CN(C)C(=O)C.[CH3:29][N:30]1[CH:34]=[CH:33][C:32]([NH:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[C:43]([OH:46])[CH:44]=3)[N:39]=[CH:38][N:37]=2)=[N:31]1>O>[CH2:1]([O:3][CH:4]([O:14][CH2:15][CH3:16])[CH2:5][O:6][C:7]1[N:12]=[CH:11][C:10]([O:46][C:43]2[CH:44]=[C:45]3[C:40](=[CH:41][CH:42]=2)[N:39]=[CH:38][N:37]=[C:36]3[NH:35][C:32]2[CH:33]=[CH:34][N:30]([CH3:29])[N:31]=2)=[CH:9][N:8]=1)[CH3:2]

Participants

Conditions

Temperature: 190 °C

Procedure

2-(2,2-Diethoxyethoxy)-5-fluoropyrimidine (168 mg, 0.73 mmol) and potassium tert-butoxide (93 mg, 0.83 mmol) were added to an N,N-dimethylacetamide solution (1 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (80 mg, 0.33 mmol), and stirred at 190° C. for 14 hours under a nitrogen atmosphere in a sealed tube. The reaction solution was cooled with ice, water was added, and extracted with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Moritex, acetone:hexane=1:2) to obtain 6-{[2-(2,2-diethoxyethoxy)pyrimidin-5-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (56 mg, yield: 37%) as a pale brown amorphous solid.

Workup

additionwas added
extractionextracted with chloroform
washThe organic layer was washed with water
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (Moritex, acetone:hexane=1:2)

Sources & evidence

ORD record: ord-34c0523900144e7eb49399c6e8f6777a
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08232284B2

Reaction notes

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