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 기록

ord-e9b2ecd37fac4b47abd246de9f8e0e20

출처 데이터셋

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05962458