Triphenylphosphine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline hydrochloride

Diethyl azodicarboxylate (315 μl, 2 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (319.5 mg, 1 mmol), (prepared as described for the starting material in Example 24), triphenylphosphine (524 mg, 2 mmol) and 2-(4-pyridyl)ethanol (160 mg, 1.25 mmol), (Zhur. Obshchei. Khim. 1958, 28, 103-110), in methylene chloride (7 ml). The mixture was stirred for 1 hour at ambient temperature and the solvent was removed by evaporation. The residue was triturated with ether, the solid collected by filtration and purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (85/10/5). The purified solid product was dissolved in a mixture of methylene chloride (50 ml) and methanol (50 ml) and 5M hydrochloric acid in isopropanol (0.5 ml) was added. After diluting with isopropanol (20 ml), the mixture was concentrated by evaporation. The precipitated solid was collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline hydrochloride (125 mg, 25%).

1. custom(prepared
2. customthe solvent was removed by evaporation
3. customThe residue was triturated with ether
4. filtrationthe solid collected by filtration
5. custompurified by column chromatography
6. washeluting with methylene chloride/acetonitrile/methanol (85/10/5)
7. dissolutionThe purified solid product was dissolved in a mixture of methylene chloride (50 ml) and methanol (50 ml) and 5M hydrochloric acid in isopropanol (0.5 ml)
8. additionwas added
9. additionAfter diluting with isopropanol (20 ml)
10. concentrationthe mixture was concentrated by evaporation
11. filtrationThe precipitated solid was collected by filtration
12. customdried under vacuum

ORDレコード

ord-7f34b0f164fb4fd79ac02ff05718481c

出典データセット

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06362336B1