Morpholine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-morpholinocarbonylpropoxy)quinazoline

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (94 mg, 4.9 mmol) was added to a mixture of 7-(3carboxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (164 mg, 0.4 mmol), morpholine (0.11 g; 1.26 mmol) and 4-dimethylaminopyridine (200 mg, 1.64 mmol) in DMF (5 ml). The reaction mixture was stirred at ambient temperature for 24 hours and the volatiles were removed by evaporation. Water was added to the residue and the aqueous mixture was extracted with methylene chloride (3×30 ml). The extracts were combined and the solvent removed by evaporation. The residue was triturated with ether and the precipitate was collected by filtration. The solid was purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (100/8/1). The purified product was triturated with acetone, collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-morpholinocarbonylpropoxy)quinazoline (88 mg, 46%).

1. customthe volatiles were removed by evaporation
2. additionWater was added to the residue
3. extractionthe aqueous mixture was extracted with methylene chloride (3×30 ml)
4. customthe solvent removed by evaporation
5. customThe residue was triturated with ether
6. filtrationthe precipitate was collected by filtration
7. customThe solid was purified by column chromatography
8. washeluting with methylene chloride/methanol/aqueous ammonia (100/8/1)
9. customThe purified product was triturated with acetone
10. filtrationcollected by filtration
11. customdried

ORD 기록

ord-51e0b028957b42e4ac8aad9798a7f1c1

출처 데이터셋

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06414148B1