Isopropanol → [4-(3-Aminophenyl)-6,7-dimethoxyquinazolin-2-yl]methylamine

Temperature

90 °C

Two hundred grams of crude 3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenylamine (content 124 g; 0.394 mol) was suspended in a mixed solution consisting of 1.2 L of tetrahydrofuran and 0.6 L of isopropanol. To the mixture was added 1.2 L of a methylamine solution in methanol, and the mixture was stirred in a SUS autoclave at 90° C. for 15 hours. The reaction mixture was allowed to cool down to 25° C., and concentrated under reduced pressure. To the residue were added 1.0 L of water and 4.0 L of chloroform, and the mixture was stirred at 50° C. for 0.5 hours and allowed to cool down to 25° C. The mixture was filtered through celite to remove the insoluble matter, and the filtrate was transferred to separatory funnel and the organic layer was separated. To the separated organic layer were added 50.0 g of anhydrous magnesium sulfate and 20.0 g of activated carbon, and the mixture was stirred at 50° C. for 1 hour and allowed to cool down to 25° C. The mixture was filtered through celite to remove the insoluble matter, and the filtrate was concentrated under reduced pressure. To the residue was added 904 mL of chloroform, and the mixture was stirred at 50° C. for 1 hour and stirred overnight after turning off the heater. Then the mixture was stirred in an ice bath for 2 hours and precipitated crystals were collected by filtration. The collected crystals were dried at 50° C. under reduced pressure to yield 76.3 g of a product of interest. Yield: 38.7%

1. temperatureto cool down to 25° C.
2. concentrationconcentrated under reduced pressure
3. additionTo the residue were added 1.0 L of water and 4.0 L of chloroform
4. stirringthe mixture was stirred at 50° C. for 0.5 hours
5. temperatureto cool down to 25° C
6. filtrationThe mixture was filtered through celite
7. customto remove the insoluble matter
8. customthe filtrate was transferred to separatory funnel
9. customthe organic layer was separated
10. additionTo the separated organic layer were added 50.0 g of anhydrous magnesium sulfate and 20.0 g of activated carbon
11. stirringthe mixture was stirred at 50° C. for 1 hour
12. temperatureto cool down to 25° C
13. filtrationThe mixture was filtered through celite
14. customto remove the insoluble matter
15. concentrationthe filtrate was concentrated under reduced pressure
16. additionTo the residue was added 904 mL of chloroform
17. stirringthe mixture was stirred at 50° C. for 1 hour
18. stirringstirred overnight
19. stirringThen the mixture was stirred in an ice bath for 2 hours
20. customprecipitated crystals
21. filtrationwere collected by filtration
22. customThe collected crystals were dried at 50° C. under reduced pressure

ORD record

ord-158a814699a84ac884425d2d5f3919d6

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07939540B2