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

HRID 1517269Notes

Reaction equation

HRID 1517269 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]([O:14][CH2:15][CH3:16])[O:11][CH2:12][CH3:13])=[CH:4][N:3]=1.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>[CH2:12]([O:11][CH:10]([O:14][CH2:15][CH3:16])[CH2:9][O:8][C:5]1[CH:4]=[N:3][C:2]([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)=[N:7][CH:6]=1)[CH3:13]

Participants

6

Reactant 4

HCID 31374DimethylacetamideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 866458972-Chloro-5-(2,2-diethoxyethoxy)pyrimidine

Product 1

HCID 684298536-{[5-(2,2-diethoxyethoxy)pyrimidin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amineYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
200 °C

Procedure

2-Chloro-5-(2,2-diethoxyethoxy)pyrimidine (225 mg, 0.91 mmol) obtained in Example 7 and potassium tert-butoxide (116 mg, 1.04 mmol) were added to an N,N-dimethylacetamide solution (1 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (100 mg, 0.42 mmol), and stirred at 200° C. for 18 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=2:3) to obtain 6-{[5-(2,2-diethoxyethoxy)pyrimidin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (177 mg, yield: 95%) as a pale orange amorphous solid.

Workup

  1. additionwas added
  2. extractionextracted with chloroform
  3. washThe organic layer was washed with 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 (Moritex, acetone:hexane=2:3)

Sources & evidence

ORD record
ord-bc4ae0890b55495da1a26e801ec06b50
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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