Potassium Carbonate → HCID 86687644, compound

HRID 1473583Notes

Reaction equation

HRID 1473583 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.[F:27][C:28]1[CH:29]=[C:30]([C:35]2[CH:40]=[CH:39][C:38](B(O)O)=[C:37]([O:44][CH3:45])[CH:36]=2)[CH:31]=[C:32]([F:34])[CH:33]=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>[F:27][C:28]1[CH:29]=[C:30]([C:35]2[CH:40]=[CH:39][C:38]([C:2]3[C:11]4[C:6](=[CH:7][C:8]([S:12]([O:15][C:16]5[C:21]([F:22])=[C:20]([F:23])[C:19]([F:24])=[C:18]([F:25])[C:17]=5[F:26])(=[O:14])=[O:13])=[CH:9][CH:10]=4)[CH:5]=[CH:4][N:3]=3)=[C:37]([O:44][CH3:45])[CH:36]=2)[CH:31]=[C:32]([F:34])[CH:33]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonateHCID 86687645HCID 86687645, compound

Product 1

HCID 86687644HCID 86687644, compoundYield 65.6%

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, 4.40 g, 10.74 mmol), (3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)boronic acid (INTERMEDIATE JJJJJ; 3.40 g, 12.89 mmol), potassium carbonate (4.45 g, 32.2 mmol), and Pd(Ph3P)4 (1.241 g, 1.074 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (40.3 ml) and water (13.42 ml) were added in sequence. The flask was fitted with a reflux condenser and lowered into 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. TLC showed two major spots. The residue was purified by chromatography on silica gel (100-g SNAP Ultra column, 0-50% EtOAc/Heptane). Fractions containing the desired product were combined and concentrated to give perfluorophenyl 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)isoquinoline-6-sulfonate (4.179 g, 7.04 mmol, 65.6% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.93 (d, J=1.6 Hz, 1H), 8.84 (d, J=5.6 Hz, 1H), 8.20 (d, J=5.7 Hz, 1H), 8.07 (dd, J=1.9, 9.0 Hz, 1H), 7.95 (d, J=8.9 Hz, 1H), 7.70-7.62 (m, 2H), 7.59-7.50 (m, 3H), 7.36-7.27 (m, 1H), 3.79 (s, 3H). m/z (ESI) 594.0 (M+H)+.

Workup

  1. customThe flask was flushed with Ar (g)
  2. addition1,4-dioxane (40.3 ml) and water (13.42 ml) were added in sequence
  3. customThe flask was fitted with a reflux condenser
  4. customlowered into a 50° C.
  5. temperatureheating bath for 1 h
  6. additionThe mixture was diluted with water
  7. extractionextracted with EtOAc (2×)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (100-g SNAP Ultra column, 0-50% EtOAc/Heptane)
  12. additionFractions containing the desired product
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-d2f656c8543f4a53ab47de905b0770e4
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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