Sodium hydride → HCID 89815042, compound

HRID 2172323Notes

Reaction equation

HRID 2172323 reaction equation
[H-].[Na+].[CH3:3][C:4]1[N:5]=[CH:6][NH:7][CH:8]=1.Br[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1F.[CH:21]1[C:30]2[C:25](=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=2)[CH:24]=[CH:23][N:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C([O-])(O)=O.[Na+]>CN(C=O)C.O.O1CCOCC1>[CH3:3][C:4]1[N:5]=[CH:6][N:7]([C:11]2[CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:10]=2[C:26]2[CH:27]=[CH:28][CH:29]=[C:30]3[C:25]=2[CH:24]=[CH:23][N:22]=[CH:21]3)[CH:8]=1

Participants

10

Reactant 6

HCID 24758Sodium hydrideHCID 62657Potassium Phosphate, TribasicHCID 1424144-Bromo-3-fluorobenzotrifluorideHCID 516892Sodium BicarbonateHCID 599474Isoquinoline-5-boronic acidHCID 178418800HCID 178418800, compound

Product 1

HCID 89815042HCID 89815042, compoundYield 49.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride 60% (0.330 g, 13.75 mmol) in 8 mL DMF was cooled to 0° C. and was treated with 4-methyl-1H-imidazole (0.676 g, 8.23 mmol). After stirring for 40 minutes, 1-bromo-2-fluoro-4-(trifluoromethyl)benzene (1.180 ml, 8.23 mmol) was added, and the reaction mixture was heated to 120° C. for 90 minutes. At this point Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.291 g, 0.412 mmol), isoquinolin-5-ylboronic acid (1.424 g, 8.23 mmol), potassium phosphate (6.99 g, 32.9 mmol), 16 mL dioxane and 12 mL water were added, and the reaction mixture was heated to 120° C. overnight. The reaction mixture was poured into saturated NaHCO3 solution and was extracted with DCM. The organics were concentrated then purified by reverse phase column chromatography [RediSep Gold C18 150 g, 15 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielding 5-(2-(4-methyl-1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)isoquinoline (1.435 g, 4.06 mmol) as an about 4:1 mixture of isomers.

Workup

  1. temperaturethe reaction mixture was heated to 120° C. for 90 minutes
  2. temperaturethe reaction mixture was heated to 120° C. overnight
  3. extractionwas extracted with DCM
  4. concentrationThe organics were concentrated
  5. customthen purified by reverse phase column chromatography [RediSep Gold C18 150 g, 15 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-56cc5a5b48354cf5884b5e7b9536eebf
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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