Potassium Carbonate → 2-[5-(2-Cyano-4-fluorophenoxy)-indazol-1-yl]-N,N-dimethylacetamide

HRID 1897502Notes

Reaction equation

HRID 1897502 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].Cl[CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:7]([C:6]1[CH:9]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[N:15]=[CH:14]2)#[N:8]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 57418753HCID 57418753, compound

Product 1

HCID 674094872-[5-(2-Cyano-4-fluorophenoxy)-indazol-1-yl]-N,N-dimethylacetamideYield 12%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-fluoro-2-(1H-indazol-5-yloxy)-benzonitrile (44d) (0.200 g, 0.790 mmol) in DMF (6 mL) was added 2-chloro-N,N-dimethylacetamide (0.115 g, 0.948 mmol) and tetrabutyl ammonium iodide (0.088 g, 0.237 mmol), followed by K2CO3 (0.164 g, 1.19 mmol). The mixture was heated to 110° C. for 48 hours under N2 atmosphere. The reaction mixture was concentrated under reduced pressure and dissolved in dichloromethane. The solution was washed with 1N HCl, filtered, and chromatographed on Biotage eluting with 5% MeOH in dichloromethane to afford 0.032 g of the product (12% yield).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutiondissolved in dichloromethane
  3. washThe solution was washed with 1N HCl
  4. filtrationfiltered
  5. customchromatographed on Biotage
  6. washeluting with 5% MeOH in dichloromethane

Sources & evidence

ORD record
ord-7c9de8d409c74e828320e50946678332
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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