6-Bromo-1-fluoronaphthalen-2-OL → 4-(6-Bromo-1-fluoro-naphthalen-2-yloxy)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline

HRID 1925257Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Br:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[C:31]([F:35])=[C:30]([OH:36])[CH:29]=[CH:28]2>CN(C1C=CN=CC=1)C.C1(C)C=CC=CC=1.CCOC(C)=O>[Br:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[C:31]([F:35])=[C:30]([O:36][C:2]1[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][CH:3]=1)[CH:29]=[CH:28]2

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline (prepared as described in WO 03/33472) (0.465 mg, 1.93 mmol), 6-bromo-1-fluoro-naphthalen-2-ol (Example 3a) (0.65 mg, 1.93 mmol) and DMAP (0.235 mg, 1.93 mmol, Aldrich) in toluene (in a microwave tube) was heated in a microwave oven (Personal Chemistry, Emrys Optimizer) at 180° C. for 2 h. The mixture was cooled to RT and diluted with 30 mL of EtOAc. The solution was washed with brine (2×10 mL), dried over Na2SO4 and concentrated in vacuo. The residue was further purified with silica gel column chromatography (40% to 100% EtOAc in hexanes) to give the title compound as an orange foam. MS (ESI, pos. ion) m/z: 541.1 (M+1). Mass Calc'd for C27H26BrFN2O4: 540.11.

Workup

temperatureThe mixture was cooled to RT
washThe solution was washed with brine (2×10 mL)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was further purified with silica gel column chromatography (40% to 100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-021d0aca3e4949f780f7eeed90a4478a
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178557B2

Reaction notes

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