Triphenylphosphine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline hydrochloride

Triphenylphosphine (615 mg, 2.3 mmol) followed by diethyl azodicarboxylate (369 μl, 2.3 mmol) were added to a solution of 4-hydroxymethyl-1-methylpiperidine (151 mg, 1.1 mmol), (J. Med. Chem. 1973, 16, 156), and 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (250 mg, 0.78 mmol), (prepared as described for the starting material in Example 7), in methylene chloride (5 ml). After stirring for 30 minutes at ambient temperature, 4-hydroxymethyl-1-methylpiperidine (51 mg, 0.39 mmol), triphenylphosphine (102 mg, 0.39 mmol) and diethyl azodicarboxylate (61 μl, 0.39 mmol) were added. After stirring for 15 minutes, the volatiles were removed under vacuum and the residue was purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (70/10/20 followed by 75/5/20 and 80/0/20). The fractions containing the expected product were combined and the volatiles were removed by evaporation. The residue was dissolved in a mixture of methylene chloride and methanol and 5M hydrogen chloride in isopropanol was added. The suspension was concentrated and the solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline hydrochloride (16 mg, 4%).

1. custom(prepared
2. stirringAfter stirring for 15 minutes
3. customthe volatiles were removed under vacuum
4. customthe residue was purified by column chromatography
5. washeluting with methylene chloride/acetonitrile/methanol (70/10/20 followed by 75/5/20 and 80/0/20)
6. additionThe fractions containing the expected product
7. customthe volatiles were removed by evaporation
8. dissolutionThe residue was dissolved in a mixture of methylene chloride and methanol and 5M hydrogen chloride in isopropanol
9. additionwas added
10. concentrationThe suspension was concentrated
11. filtrationthe solid was collected by filtration
12. washwashed with ether
13. customdried under vacuum

ORD 기록

ord-018227f29e6540f9acb1920c84888081

출처 데이터셋

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09040548B2