Azidotrimethylsilane → 3-Chloro-6-(2H-1,2,3-triazol-4-yl)isoquinoline

HRID 523062Notes

Reaction equation

HRID 523062 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C:12]#[CH:13])=[CH:7][CH:6]=2.[N:14]([Si](C)(C)C)=[N+:15]=[N-:16]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C:12]1[CH:13]=[N:16][NH:15][N:14]=1)=[CH:7][CH:6]=2

Participants

5

Reactant 2

HCID 78378AzidotrimethylsilaneHCID 899955703-Chloro-6-ethynylisoquinoline

Product 1

HCID 899956273-Chloro-6-(2H-1,2,3-triazol-4-yl)isoquinolineYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

3-chloro-6-ethynylisoquinoline (Preparation 50, 120 mg, 0.64 mmol) was dissolved in dry DMF (1 mL). Azidotrimethylsilane (1 mL, 7.5 mmol) was added and the reaction stirred at 120° C. for 2 hours. The reaction was cooled to room temperature and diluted with ethyl acetate (20 mL). The organic solution was washed with water (20 mL), brine (20 mL), dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 2% 7N NH3 in methanol in DCM followed by elution through an SCX-2 column using 50% methanol in chloroform followed by 50% 7N NH3 in methanol in chloroform to afford the title compound as a pale brown powder (90 mg, 61%).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washThe organic solution was washed with water (20 mL), brine (20 mL)
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified
  6. washeluting with 2% 7N NH3 in methanol in DCM
  7. washfollowed by elution through an SCX-2 column

Sources & evidence

ORD record
ord-c19af088cac24e75b2d62f82f2dc7351
Source dataset
uspto-grants-2016_05
Patent number
US09334286B2

Reaction notes

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