5-Chloro-7-{[methoxy(methyl)amino]carbonyl}quinolin-8-yl trifluoromethanesulfonate → 5-chloro-8-(3-fluorophenyl)-N-methoxy-N-methylquinoline-7-carboxamide

HRID 1192507Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:8]([C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.[F:26][C:27]1[CH:28]=[C:29]([Zn]I)[CH:30]=[CH:31][CH:32]=1>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:17][C:10]1[CH:9]=[C:8]([C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])[C:7]([C:31]2[CH:30]=[CH:29][CH:28]=[C:27]([F:26])[CH:32]=2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 5-chloro-7-{[methoxy(methyl)amino]carbonyl}quinolin-8-yl trifluoromethanesulfonate (0.200 g, 0.502 mmol) in tetrahydrofuran (5 mL) was added 0.50 M (3-fluorophenyl)(iodo)zinc in tetrahydrofuran (1.20 mL, 0.602 mmol) with stirring, followed by addition of tetrakis(triphenylphosphine)palladium(0) (29.0 mg, 0.0251 mmol). The reaction mixture was heated at 60° C. overnight. After cooling to room temperature, the mixture was filtered and concentrated under reduced pressure. The crude mixture was purified on silica gel, eluting with 0 to 60% EtOAc in hexane, to give the desired product (154 mg, 89%). LCMS calculated for C18H15ClFN2O2(M+H)+: m/z=345.1; found: 345.0.

Workup

temperatureAfter cooling to room temperature
filtrationthe mixture was filtered
concentrationconcentrated under reduced pressure
customThe crude mixture was purified on silica gel
washeluting with 0 to 60% EtOAc in hexane

Sources & evidence

ORD record: ord-13d2fa1fdd624155beec2810c72b9aaf
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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