4-Chloro-6,7-dimethoxyquinoline → N-(1-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-5-oxopyrrolidin-3-yl)benzamide

HRID 1993383Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:16][C:17]1[CH:18]=[C:19]([N:24]2[C:28](=[O:29])[CH2:27][CH:26]([NH:30][C:31](=[O:38])[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:25]2)[CH:20]=[CH:21][C:22]=1[OH:23]>CN(C1C=CN=CC=1)C.O1CCOCC1.CCOC(C)=O>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[O:23][C:22]1[CH:21]=[CH:20][C:19]([N:24]2[C:28](=[O:29])[CH2:27][CH:26]([NH:30][C:31](=[O:38])[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:25]2)=[CH:18][C:17]=1[F:16]

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 4-chloro-6,7-dimethoxyquinoline (0.14 g, 0.6 mmol), N-(1-(3-fluoro-4-hydroxyphenyl)-5-oxopyrrolidin-3-yl)benzamide (Step 4, 0.20 g, 0.6 mmol) and DMAP (78 mg, 0.6 mmol) in 2 mL of dioxane (in a microwave tube) was heated in a microwave (Personal Chemistry, Emrys Optimizer) at 160° C. for 1 h. The mixture was cooled to RT and diluted with 50 mL of EtOAc. The solution was washed with 20 mL of satd. NaHCO3 followed by 20 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography (50% to 100% EtOAc in hexanes then to 5% MeOH/EtOAc) to provide a white solid. MS (ESI pos. ion) m/z: 502.3 (M+H). Calc'd Exact Mass for C28H24FN3O5: 501.51.

Workup

temperatureThe mixture was cooled to RT
washThe solution was washed with 20 mL of satd
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by chromatography (50% to 100% EtOAc in hexanes
customto 5% MeOH/EtOAc) to provide a white solid

Sources & evidence

ORD record: ord-a0adff82b2f84b8eade9f12d77f0983a
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652009B2

Reaction notes

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