7-(benzyloxy)-N-(4-bromo-2-fluorophenyl)-6-methoxyquinazolin-4-amine

Hydrogen chloride (6.5 M, 2.54 mL) was added to a mixture of compound 1 (4.51 g, 15.0 mmol) and 4-chloro-2-fluoroaniline (2.40 g, 16.5 mmol) in 2-propanol (160 mL), then the mixture was heated at reflux for 2 h. The mixture was cooled and solid was filtered. The solid was then washed with 2-propanol, followed by Et2O, and dried under vacuum overnight to give 2a (7.9 g, 94percent) as a white solid.A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline (8. 35g, 27.8mmol) and 4- bromo-2-fluoroaniline (5.65g, 29. 7MMOL) in 2-propanol (200ML) was heated at reflux for 4 hours. The resulting precipitate was collected by filtration, washed with 2-propanol and then ether and dried under vacuum to give 7-BENZYLOXY-4- (4-BROMO-2-FLUOROANILINO)-6- methoxyquinazoline hydrochloride (9.46g, 78percent). 1H NMR Spectrum: (DMSOd6; CD3COOD) 4.0 (s, 3H); 5.37 (s, 2H); 7.35-7. 5 (M, 4H); 7.52- 7.62 (m, 4H); 7. 8 (d, 1H); 8. 14 (9s, 1H); 8.79 (s, 1H) MS-ESI: 456 [MH] + Elemental analysis: Found C 54.0 H 3.7 N 8.7 C22HI7N302BRF 0. 9HC1 Requires C 54.2 H 3.7 N 8. 6percent4-Bromo-2-fluorobenzenamine (3.1 g, 16.1 mmol, 1.10 equiv) was added to a solution of 7-(benzyloxy)-4-chloro-6-methoxyquinazoline (4.5 g, 12 mmol, 1.00 equiv) and isopropyl alcohol (100 mL). (7-Benzyloxy-6-methoxyquinazolin-4-yl)-(4-bromo-2-fluorophenyl)- amine A mixture of 2-2 (7-benzyloxy-4-chloro-6-methoxyquinazoline, obtained from J. W. Pharmlab, 2.05 g, 6.81 mmol) and 4-bromo-2-fluoroaniline (3.04 g, 15.9 mmol) was heated to reflux in isopropyl alcohol (80 mL) for 24 hours. After cooling to room temperature, the mixture was made basic with sodium bicarbonate (1.0 g) in DIUF water (10 mL). The mixture was concentrated under reduced pressure and dried under high vacuum before purification by flash column chromatography on silica gel (80 g), eluting with 1-10percent methanol in dichloromethane. The procedure produced 2-3 as a light yellow solid (1.37 g, 45percent yield). (at)H NMR (300 MHz, DMSO-d6): 6 9.48 (s, 1H), 8.33 (s, 1H), 7.80 (s, 1H), 7.56-7.33 (m, 8H), 7.26 (s, 1 H), 5.26 (s, 2H), 3.94 (s, 3H). The compound obtained in

Molecular Weight:454.3
XLogP3:5.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:6
Exact Mass:453.04882
Monoisotopic Mass:453.04882
Topological Polar Surface Area:56.3
Heavy Atom Count:29
Complexity:510
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes