Isopropylamine → 8-bromo-3-cyclopropyl-7-fluoro-2-(isopropylamino)quinazolin-4(3H)-one
Reaction equation
[Br:1][C:2]1[C:3]([F:17])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]([CH:13]1[CH2:15][CH2:14]1)[C:7]2=[O:16].[CH:18]([NH2:21])([CH3:20])[CH3:19]>CN1C(=O)CCC1>[Br:1][C:2]1[C:3]([F:17])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:21][CH:18]([CH3:20])[CH3:19])[N:8]([CH:13]1[CH2:15][CH2:14]1)[C:7]2=[O:16]Participants
4
Procedure
A slurry of 8-bromo-2-chloro-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (721; 0.080 g, 0.252 mmol) in isopropylamine (Aldrich; 0.541 ml, 6.30 mmol) and 0.2 mL NMP was heated in a sealed tube in a biotage initiator microwave to 100° C. for 20 min. The reaction was partitioned between water and EtOAc. The organic layer was washed with water once, satd aq NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 8-bromo-3-cyclopropyl-7-fluoro-2-(isopropylamino)quinazolin-4(3H)-one (0.079 g, 0.232 mmol, 92% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.89 (1H, dd, J=8.8, 6.5 Hz), 7.01 (1H, t, J=8.7 Hz), 6.85 (1H, d, J=7.6 Hz), 4.41 (1H, dq, J=13.6, 6.7 Hz), 2.64-2.79 (1H, m), 1.30 (6H, d, J=6.7 Hz), 1.19-1.27 (2H, m), 0.71-0.79 (2H, m). m/z (ESI, +ve ion) 340.0/342.0 (M+H)+.