Potassium Carbonate → Perfluorophenyl 1-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)isoquinoline-6-sulfonate

HRID 1473542Notes

Reaction equation

HRID 1473542 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([O:15][C:16]3[C:21]([F:22])=[C:20]([F:23])[C:19]([F:24])=[C:18]([F:25])[C:17]=3[F:26])(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[Cl:27][C:28]1[CH:33]=[C:32](B(O)O)[C:31]([O:37][CH3:38])=[CH:30][C:29]=1[C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=1.C(=O)([O-])[O-].[K+].[K+]>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:27][C:28]1[CH:33]=[C:32]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([S:12]([O:15][C:16]4[C:21]([F:22])=[C:20]([F:23])[C:19]([F:24])=[C:18]([F:25])[C:17]=4[F:26])(=[O:14])=[O:13])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)[C:31]([O:37][CH3:38])=[CH:30][C:29]=1[C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonateHCID 86687599(2-Chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)boronic acid

Product 1

HCID 86687601Perfluorophenyl 1-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)isoquinoline-6-sulfonateYield 80%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
50 °C

Procedure

A round-bottom flask was charged with perfluorophenyl 1-chloroisoquinoline-6-sulfonate (from Step 1 of Example 73, 500 mg, 1.220 mmol), (2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)boronic acid (Intermediate SSSS; 479 mg, 1.709 mmol) potassium carbonate (506 mg, 3.66 mmol), and Pd(Ph3P)4 (141 mg, 0.122 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (4576 μl) and water (1525 μl) were added. The flask was fitted with a reflux condenser and heated in a 50° C. heating bath for 40 min. The mixture was partitioned between water and EtOAc. The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 25-g silica gel loading column, 0-50% EtOAc/Heptane) to give perfluorophenyl 1-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)isoquinoline-6-sulfonate (593.7 mg, 0.973 mmol, 80% yield) as a white foam. m/z (ESI) 609.9 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (4576 μl) and water (1525 μl) were added
  3. customThe flask was fitted with a reflux condenser
  4. temperatureheating bath for 40 min
  5. customThe mixture was partitioned between water and EtOAc
  6. customThe layers were separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 25-g silica gel loading column, 0-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-691a1a73e6a3431c8082be1c07c21e09
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…