Hydrochloric Acid → 4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline

温度

0 °C

To a solution of 4.22 ml of N,N-diisopropylamine in tetrahydrofuran (25 ml) cooled to −78° C. was added dropwise 18.8 ml of 1.6 mol/L n-BuLi hexane solution. After completion of addition, a temperature was elevated to 0° C., and the mixture was stirred at 0° C. for 20 minutes, and cooled again to −78° C. 1.33 ml of 2-bromo-1-propene in tetrahydrofuran (25 ml) was added, and the mixture was stirred at −78° C. for 2 hours. To the mixture was added dropwise a solution of 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methoxy methyl amide (XI-1, 2.33 g) in tetrahydrofuran (50 ml) and, after completion of addition, a temperature was elevated to 0° C., followed by stirring for 3 hours. After completion of the reaction, the reaction mixture was poured into ice water, neutralized with 2 mol/L hydrochloric acid, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, the filtrate was concentrated, and the resulting crystalline residue was washed with methylene chloride to obtain 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline (VII-4, 1.71 g) as a yellow solid.

1. additionAfter completion of addition
2. customwas elevated to 0° C.
3. temperaturecooled again to −78° C
4. stirringthe mixture was stirred at −78° C. for 2 hours
5. additionafter completion of addition
6. customwas elevated to 0° C.
7. stirringby stirring for 3 hours
8. customAfter completion of the reaction
9. extractionextracted with ethyl acetate
10. dry with materialThe organic layer was dried over sodium sulfate
11. concentrationthe filtrate was concentrated
12. washthe resulting crystalline residue was washed with methylene chloride

ORDレコード

ord-7c2e73f97f324c1d9c7ca8b831f25cf6

出典データセット

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08202879B2