6-Bromo4-(3-chloro-4-fluoroanilino)quinazoline hydrochloride salt → HCID 9956298, compound
Reaction equation
Cl.Br[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]=[C:6]2[NH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=1.[O:22]1[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][C:30]2[S:34][C:33](B(OC(C)C)OC(C)C)=[CH:32][CH:31]=2)[CH2:24][CH2:23]1>>[Cl:21][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=1[F:20])[NH:13][C:6]1[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:33]3[S:34][C:30]([CH2:29][CH2:28][N:25]4[CH2:26][CH2:27][O:22][CH2:23][CH2:24]4)=[CH:31][CH:32]=3)[CH:4]=2)[N:9]=[CH:8][N:7]=1Participants
3
Procedure
Using an analogous procedure to that described in Example 5 except that the reaction mixture was heated to reflux for 4 hours, 6-bromo-4-(3-chloro-4-fluoroanilino)quinazoline hydrochloride salt was reacted with di-isopropyl 5-(2-morpholinoethyl)thien-2-ylboronate. The reaction mixture was cooled to ambient temperature and partitioned between methylene chloride and water. The organic phase was washed with brine, dried (MgSO4) and evaporated. The residue was triturated under a mixture of hexane and ethyl acetate to give 4-(3-chloro-4-fluoroanilino)-6-[5-(2-morpholinoethyl)thien-2-yl]quinazoline in 27% yield;