Cesium fluoride → ethyl 8-(4-amino-2,5-difluoro-phenyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

HRID 1478343Notes

Reaction equation

Cl[C:2]1[C:3]([F:22])=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]2=[O:21].[F:23][C:24]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[C:28]([F:40])=[CH:27][C:25]=1[NH2:26].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:26][C:25]1[C:24]([F:23])=[CH:30][C:29]([C:2]2[C:3]([F:22])=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]3=[O:21])=[C:28]([F:40])[CH:27]=1

Participants

Conditions

Temperature: 85 °C

Procedure

Ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (100 mg, 0.32 mmol), 2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-aniline (667 mg, 2.06 mmol), tricyclohexylphosphine (105 mg, 0.41 mmol) and cesium fluoride (482 mg, 3.2 mmol) were added to ACN (5 mL). The reaction mixture was degassed with argon. Palladium(II) acetate (24 mg, 0.11 mmol) was added. The reaction mixture was heated at 85° C. for 2 h. The reaction mixture was cooled and evaporated in vacuum. Purification by flash silica column chromatography (DCM:MeOH) (1:0 to 9:1) afforded the title compound as a yellow solid (100 mg, 35%).

Workup

customThe reaction mixture was degassed with argon
temperatureThe reaction mixture was cooled
customevaporated in vacuum
customPurification by flash silica column chromatography (DCM:MeOH) (1:0 to 9:1)

Sources & evidence

ORD record: ord-ab44a33b63cc40bab74ffde5678b426b
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403818B2

Reaction notes

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