[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].Cl.[CH3:19][C:20]1([NH2:23])[CH2:22][CH2:21]1.C(N(CC)CC)C>CS(C)=O.O>[Br:1][C:2]1[C:3]([F:17])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:23][C:20]1([CH3:19])[CH2:22][CH2:21]1)[N:8]([CH:13]1[CH2:15][CH2:14]1)[C:7]2=[O:16]A glass microwave reaction vessel was charged with 8-bromo-2-chloro-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (721) (125 mg, 0.394 mmol) and 1-methylcyclopropanamine hydrochloride (127 mg, 1.18 mmol, Small Molecules Inc.) in DMSO (1.0 mL) followed by triethylamine (0.16 mL, 1.18 mmol). The reaction mixture was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 1 h. The mixture was diluted with water (20 mL) and extracted with DCM (30 mL×4). The combined organic layers were washed with water (15 mL), dried (MgSO4), filtered and concentrated. The residue was triturated with hexanes and filtered to give the crude product 96 mg. MS (ESI, pos. ion) m/z: 352 (M+1); 1H NMR (400 MHz, CDCl3) δ ppm 8.03 (1H, dd, J=8.8, 6.1 Hz), 6.90 (1H, t, J=8.4 Hz), 2.65-2.74 (1H, m), 1.61 (3H, s), 1.30-1.37 (2H, m), 0.83-0.96 (6H, m).
Wird geladen…
