Potassium Carbonate → HCID 86687635, compound

HRID 1473575Notes

Reaction equation

HRID 1473575 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[C:33]([F:34])=[CH:32][C:31](B(O)O)=[C:30]([O:38][CH3:39])[CH:29]=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[C:33]([F:34])=[CH:32][C:31]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([S:12]([O:15][C:16]4[C:17]([F:26])=[C:18]([F:25])[C:19]([F:24])=[C:20]([F:23])[C:21]=4[F:22])(=[O:13])=[O:14])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[C:30]([O:38][CH3:39])[CH:29]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonateHCID 86687636HCID 86687636, compound

Product 1

HCID 86687635HCID 86687635, compoundYield 85.3%

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 (see EXAMPLE 73, STEP 1, 1.7 g, 4.15 mmol), (4-chloro-5-fluoro-2-methoxyphenyl)boronic acid (INTERMEDIATE FFFFF; 1.272 g, 6.22 mmol), potassium carbonate (1.720 g, 12.45 mmol), and Pd(PPh3)4 (0.479 g, 0.415 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (15.56 ml) and water (5.19 ml) were added. The flask was fitted with a reflux condenser and heated in a 50° C. heating bath for 1 h. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 0-50% EtOAc/Heptane) to give perfluorophenyl 1-(4-chloro-5-fluoro-2-methoxyphenyl)isoquinoline-6-sulfonate (1.89 g, 3.54 mmol, 85% yield) as a white foam. m/z (ESI) 534.0 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (15.56 ml) and water (5.19 ml) were added
  3. customThe flask was fitted with a reflux condenser
  4. temperatureheating bath for 1 h
  5. additionThe mixture was diluted with water
  6. extractionextracted with EtOAc (2×)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 0-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-028c1aa50afb4affbbb875585ce70669
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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