Tetrahydrofuran → 6-(3-{[3-(1-Cyano-1-methylethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazine-2-carboxylic acid

To a mixture of 3-(1-cyano-1-methylethyl)benzoic acid (454 mg, 2.40 mmol), tetrahydrofuran (10 mL) and N,N-dimethylformamide (0.01 mL) was added oxalyl chloride (366 mg, 2.88 mmol), and the mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure, tetrahydrofuran was added to the residue, and the mixture was azeotroped twice. The residue was dissolved in N-methylpyrrolidone (4 mL), added to a solution of ethyl 6-(3-aminophenoxy)imidazo[1,2-b]pyridazine-2-carboxylate (350 mg, 1.17 mmol) in N-methylpyrrolidone (6 mL), and the mixture was stirred at room temperature for 2 hr. Ethyl acetate was added to the reaction mixture, and the mixture was washed with saturated aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate, and filtrated. To the residue were added 8N aqueous sodium hydroxide solution (4.0 mL) and methanol (10.0 mL), and the mixture was stirred at room temperature for 10 min. 6N Hydrochloric acid (5.0 mL) and water (60 mL) were added to the mixture, and the mixture was extracted with ethyl acetate (150 mL). The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was washed with hexane to give the title compound (828 mg, 94%) as a white powder.

1. customThe solvent was evaporated under reduced pressure, tetrahydrofuran
2. additionwas added to the residue
3. customthe mixture was azeotroped twice
4. dissolutionThe residue was dissolved in N-methylpyrrolidone (4 mL)
5. stirringthe mixture was stirred at room temperature for 2 hr
6. washthe mixture was washed with saturated aqueous sodium hydrogencarbonate solution
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltrated
9. additionTo the residue were added 8N aqueous sodium hydroxide solution (4.0 mL) and methanol (10.0 mL)
10. stirringthe mixture was stirred at room temperature for 10 min
11. addition6N Hydrochloric acid (5.0 mL) and water (60 mL) were added to the mixture
12. extractionthe mixture was extracted with ethyl acetate (150 mL)
13. dry with materialThe extract was dried over anhydrous magnesium sulfate
14. customthe solvent was evaporated under reduced pressure
15. washThe residue was washed with hexane

ORD 기록

ord-63eecded4a0148b69f81da2fb595abc6

출처 데이터셋

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08034812B2