1,2-Dibromoethane → N-(4-{[7-(2-bromoethoxy)-6-methoxy-4-quinazolinyl]-oxy}-2-chlorophenyl)-N'-propylurea

N-{2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N′-propylurea (72 mg), potassium carbonate (30 mg), and 1,2-dibromoethane (62 μl) were dissolved in N,N-dimethylformamide (4 ml), and the solution was stirred at room temperature for 3 hr. The solvent was removed by distillation under the reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was washed with ether to give 40 mg (yield 45%) of N-(4-{[7-(2-bromoethoxy)-6-methoxy-4-quinazolinyl]-oxy}-2-chlorophenyl)-N′-propylurea as an intermediate. The intermediate (45 mg), potassium carbonate (30 mg), and morpholine (80 μl) were dissolved in N,N-dimethylformamide (2 ml), and the solution was stirred at room temperature overnight. The solvent was removed by distillation under the reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform/methanol to give 42 mg (yield 56%) of the title compound.

1. customThe solvent was removed by distillation under the reduced pressure
2. additionWater was added to the residue
3. extractionthe mixture was extracted with chloroform
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. customThe solvent was removed by distillation under the reduced pressure
6. washThe residue was washed with ether

ORD record

ord-c02daafe4b2840b3ab17ec6ecffd4e55

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07169789B2