Potassium Phosphate, Tribasic → Methyl 8-fluoro-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate

HRID 922805Notes

Reaction equation

Br[C:2]1[C:11]2[C:6](=[C:7]([F:13])[C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[CH:3]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[F:13][C:7]1[C:8]([CH3:12])=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[CH:3]=[C:2]2[C:22]1[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=1

Participants

Conditions

Temperature: 100 °C

Procedure

After degassing with N2, a mixture of methyl 4-bromo-8-fluoro-7-methylquinoline-2-carboxylate (7-16, 650 mg, 2.18 mmol.), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (544 mg, 2.62 mmol) Pd(dppf)Cl2—CH2Cl2 adduct (89 mg, 0.11 mmol), and K3PO4 (1388 mg, 6.54 mmol) in 1,4-dioxane (12.9 mL) and H2O (1.6 mL) was heated at 100° C. for 20 min under microwave condition. After cooling to room temperature, the reaction mixture was filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexane (0-100%) to afford methyl 8-fluoro-7-methyl-4-(1-methyl-1H-pyrazol-4-yl)quinoline-2-carboxylate (7-17, 481 mg, 74%). LRMS m/z (M+H)+ 300.3 found, 300.1 require.

Workup

customAfter degassing with N2
temperatureAfter cooling to room temperature
filtrationthe reaction mixture was filtered
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel
washeluting with EtOAc/Hexane (0-100%)

Sources & evidence

ORD record: ord-96421acf1b424138b0871aa46a14180e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278960B2

Reaction notes

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