Sodium Chloride → N-[3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenyl]formamide

온도

60 °C

To a mixture of 2.00 g (7.72 mmol) of 2,4-dichloro-6,7-dimethoxyquinazoline, 2.38 g (9.26 mmol) of N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]formamide, tetrahydrofuran (50 mL), and 2 M aqueous sodium carbonate solution (10 mL) were added palladium acetate (17.7 mg) and 1,1′-bis(diphenylphosphino)ferrocene (42.8 mg) in this order, and the mixture was stirred at 60° C. for 6 hours. The mixture was allowed to cool, then 5% w/w sodium chloride solution (50 mL) and ethyl acetate (50 mL) were added followed by stirring for 5 minutes, and the insoluble matter was collected by filtration. The filtrate was transferred to a separatory funnel to extract the organic layer. The organic layer was washed twice with 5% w/w sodium chloride solution (50 mL) and then concentrated under reduced pressure. To the concentration residue were added 2-propanol (15 mL) and ethyl acetate (10 mL), and the mixture was suspended by stirring at 50° C. for 2 hours. The suspension was allowed to cool, and then the precipitated crystals were collected by filtration and dried to give 667 mg of a target product. Meanwhile, the insoluble matter collected by filtration was dissolved in a mixed solution of dichloromethane/methanol (300 mL/100 mL), the mixture was filtered to remove the insoluble matter, and the filtrate was concentrated under reduced pressure. To the concentration residue were added 2-propanol (15 mL) and ethyl acetate (10 mL), and the mixture was suspended by stirring at 50° C. for 2 hours. The mixture was allowed to cool, and then the precipitated crystals were collected by filtration and dried to give 1.78 g of a target product. A total of 2.45 g was yielded, and the yield was 91.3%.

1. temperatureto cool
2. stirringby stirring for 5 minutes
3. filtrationthe insoluble matter was collected by filtration
4. customThe filtrate was transferred to a separatory funnel
5. extractionto extract the organic layer
6. washThe organic layer was washed twice with 5% w/w sodium chloride solution (50 mL)
7. concentrationconcentrated under reduced pressure
8. additionTo the concentration residue were added 2-propanol (15 mL) and ethyl acetate (10 mL)
9. stirringby stirring at 50° C. for 2 hours
10. temperatureto cool
11. filtrationthe precipitated crystals were collected by filtration
12. customdried

ORD 기록

ord-5ed6f966a4ca4bdd98c73752a2e1f914

출처 데이터셋

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08492543B2