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

Temperature

50 °C

To 354 mg (1.00 mmol) of N-[3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenyl]formamide, tetrahydrofuran (2.06 mL), and methanol (1.03 mL) was added a methanol solution (2.06 mL) of 40% methylamine, and the mixture was reacted at 90° C. for 12 hours. The reaction mixture was allowed to cool and then poured into a mixed solution of ethyl acetate (30 mL), tetrahydrofuran (30 mL), and 5% w/w sodium chloride solution (30 mL) to extract the organic layer. The organic layer was washed with 5% w/w sodium chloride solution (30 mL) and then concentrated under reduced pressure. To the concentration residue was added ethyl acetate (1.5 mL), and the mixture was crystallized with a spatula followed by stirring at 50° C. for 1.5 hours. To this suspension was dropwise added t-butyl methyl ether (1.5 mL), and the mixture was further stirred for 1 hour and allowed to cool gradually. The precipitated crystals were collected by filtration and dried to give 288 mg of a target product (yield: 90.5%).

1. customthe mixture was reacted at 90° C. for 12 hours
2. temperatureto cool
3. extractionto extract the organic layer
4. washThe organic layer was washed with 5% w/w sodium chloride solution (30 mL)
5. concentrationconcentrated under reduced pressure
6. additionTo the concentration residue was added ethyl acetate (1.5 mL)
7. customthe mixture was crystallized with a spatula
8. stirringthe mixture was further stirred for 1 hour
9. temperatureto cool gradually
10. filtrationThe precipitated crystals were collected by filtration
11. customdried

ORD record

ord-99ee1a5fbd6c42339e1539ff66dd7b51

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08492543B2