Triethylamine → 8-bromo-3-cyclopropyl-7-fluoro-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-one

HRID 1056381Notes

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].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]

Participants

Conditions

Temperature: 100 °C

Procedure

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).

Workup

customA glass microwave reaction vessel
extractionextracted with DCM (30 mL×4)
washThe combined organic layers were washed with water (15 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe residue was triturated with hexanes
filtrationfiltered

Sources & evidence

ORD record: ord-8769e97d10ee4908a3baa8720ef5b29f
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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