Potassium Phosphate, Tribasic → 6-(benzylthio)-1-(2,3'-difluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-one

HRID 1504403Notes

Reaction equation

HRID 1504403 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[CH:24]=[C:23]([F:25])[C:22](Br)=[CH:21][C:20]=1[O:27][CH3:28])[C:14](=[O:29])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCOC(C)=O.CCCCCCC>[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[C:20]([O:27][CH3:28])=[CH:21][C:22]([C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([F:30])[CH:36]=3)=[C:23]([F:25])[CH:24]=1)[C:14](=[O:29])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 1177370446-(benzylthio)-1-(4-bromo-5-fluoro-2-methoxyphenyl)quinolin-2(1H)-one

Product 1

HCID 1177369956-(benzylthio)-1-(2,3'-difluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-oneYield 74.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
90 °C

Procedure

A vial was charged with 6-(benzylthio)-1-(4-bromo-5-fluoro-2-methoxyphenyl)quinolin-2(1H)-one (0.200 g, 0.425 mmol), (3-fluorophenyl)boronic acid (0.065 g, 0.468 mmol), potassium phosphate, dibasic (0.296 g, 1.701 mmol), and PdCl2(dppf) (0.031 g, 0.043 mmol)). The vial was flushed with Ar (g), then 1,4-dioxane (1.134 ml) and water (0.567 ml) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h at 90° C. LCMS showed clean desired product. The mixture was extracted with EtOAc (3×), then the combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50%, then 50-100% EtOAc/Heptane) to give 6-(benzylthio)-1-(2,3′-difluoro-5-methoxy-[1,1′-biphenyl]-4-yl)quinolin-2(1H)-one (0.154 g, 0.317 mmol, 74.6% yield). m/z (ESI) 486.0 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (1.134 ml) and water (0.567 ml) were added
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (3×)
  5. concentrationthe combined organic extracts were concentrated
  6. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50%

Sources & evidence

ORD record
ord-4385530a68e14192ba94416e72031281
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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