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

HRID 1473441Notes

Reaction equation

HRID 1473441 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.[C:27]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[C:31]([O:38][CH3:39])[CH:30]=1)#[N:28].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>[C:27]([C:29]1[CH:34]=[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:38][CH3:39])[CH:30]=1)#[N:28]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 532162964-Cyano-2-methoxyphenylboronic acidHCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonate

Product 1

HCID 86687486Perfluorophenyl 1-(4-cyano-2-methoxyphenyl)isoquinoline-6-sulfonateYield 66.5%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A vial was charged with perfluorophenyl 1-chloroisoquinoline-6-sulfonate (see Example 73, Step 1) (210 mg, 0.513 mmol), (4-cyano-2-methoxyphenyl)boronic acid (181 mg, 1.025 mmol), potassium carbonate (213 mg, 1.538 mmol), and Pd(Ph3P)4 (59.2 mg, 0.051 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (1922 μl) and water (641 μl) were added. The vial was sealed and placed in a 50° C. heating bath for 1.5 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were concentrated. The crude product was purified by chromatography on silica gel (40-g column with 0 to 40% EtOAc/Heptane) to give perfluorophenyl 1-(4-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate (172.6 mg, 0.341 mmol, 66.5% yield) as a white foam: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.86 (d, J=5.7 Hz, 1H), 8.61 (d, J=2.0 Hz, 1H), 7.99 (dd, J=2.0, 8.9 Hz, 1H), 7.91-7.82 (m, 2H), 7.61-7.57 (m, 1H), 7.54-7.47 (m, 1H), 7.34 (d, J=1.4 Hz, 1H), 3.77 (s, 3H); m/z (ESI) 507.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (1922 μl) and water (641 μl) were added
  3. customThe vial was sealed
  4. customplaced in a 50° C.
  5. temperatureheating bath for 1.5 h
  6. additionThe mixture was diluted with water
  7. extractionextracted with EtOAc (3×)
  8. concentrationThe combined organic extracts were concentrated
  9. customThe crude product was purified by chromatography on silica gel (40-g column with 0 to 40% EtOAc/Heptane)

Sources & evidence

ORD record
ord-8f7e24fd96a543aeaf7aed9b838e1295
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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