Potassium Carbonate → Perfluorophenyl 1-(4-chloro-5-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate

HRID 1473550Notes

Reaction equation

HRID 1473550 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:35]=[C:34]([O:36][CH3:37])[C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][C:29]=1[C:30]#[N:31].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:29]([C:30]#[N:31])=[CH:32][C:33]([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:14])=[O:13])=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[C:34]([O:36][CH3:37])[CH:35]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonateHCID 866876072-Chloro-4-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)benzonitrile

Product 1

HCID 86687608Perfluorophenyl 1-(4-chloro-5-cyano-2-methoxyphenyl)isoquinoline-6-sulfonateYield 80%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A round-bottom flask was charged with perfluorophenyl 1-chloroisoquinoline-6-sulfonate (see EXAMPLE 73, Step 1; 555 mg, 1.355 mmol), 2-chloro-4-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (INTERMEDIATE UUUU, 477 mg, 1.626 mmol), potassium carbonate (562 mg, 4.06 mmol), and Pd(Ph3P)4 (157 mg, 0.135 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (5080 μl) and water (1693 μl) were added. The flask was lowered into a 50° C. heating bath for 1 h. The reaction mixture was diluted with water and EtOAc. The organic extract was 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-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate (583.89 mg, 1.080 mmol, 80% yield) as an off-white foam. m/z (ESI) 540.9 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (5080 μl) and water (1693 μl) were added
  3. customwas lowered into a 50° C.
  4. temperatureheating bath for 1 h
  5. additionThe reaction mixture was diluted with water and EtOAc
  6. extractionThe organic extract
  7. dry with materialwas 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-f40e1327955d451ba949158f1d806f31
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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