Water → 7-(6-Fluoro-4-methylpyridin-3-yl)isoquinolin-3-amine

HRID 468926Notes

Reaction equation

HRID 468926 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH2:12])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[F:13][C:14]1[N:19]=[CH:18][C:17](B(O)O)=[C:16]([CH3:23])[CH:15]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.O>C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:13][C:14]1[N:19]=[CH:18][C:17]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH2:12])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)=[C:16]([CH3:23])[CH:15]=1

Participants

8

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 441182432-Fluoro-4-methylpyridine-5-boronic acidHCID 529877577-Bromoisoquinolin-3-amine

Product 1

HCID 711151637-(6-Fluoro-4-methylpyridin-3-yl)isoquinolin-3-amineYield 83.5%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-bromoisoquinolin-3-amine (410.5 mg; 1.840 mmol), (6-fluoro-4-methyl-3-pyridyl)boronic acid (374.1 mg; 2.414 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (70.4 mg; 0.0994 mmol), potassium carbonate (624.3 mg; 4.517 mmol), dioxane (6.0 mL; 70 mmol) and water (0.6 mL; 30 mmol) was subjected to microwave irradiation at 120° C. for 40 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 20-100% ethyl acetate in dichloromethane) to yield 389.0 mg (83%) of the title compound. LCMS (ESI): M+H=254.2.

Workup

  1. customirradiation at 120° C. for 40 minutes
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 20-100% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-60042a196d054db9bcd2559bc17bc41a
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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