1H-Indazole → HCID 59743345, compound

HRID 1947012Notes

Reaction equation

HRID 1947012 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[H-].[Na+].Cl[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([S:19][CH3:20])[N:14]=1>CN(C=O)C>[CH3:20][S:19][C:15]1[N:16]=[C:17]([N:2]2[CH:3]=[C:4]3[C:9]([CH:8]=[CH:7][CH:6]=[CH:5]3)=[N:1]2)[CH:18]=[CH:13][N:14]=1

Participants

5

Reactant 3

HCID 92211H-IndazoleHCID 24758Sodium hydrideHCID 971134-Chloro-2-methylthiopyrimidine

Product 1

HCID 59743345HCID 59743345, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1H-indazole (2.36 g, 20.0 mmol) in anhydrous DMF (100 mL) was treated with NaH (60% dispersion in mineral oil, 1.60 g, 40.0 mmol) at RT for 10 min. 4-Chloro-2-methylthiopyrimidine (2.55 ml, 22.0 mmol) was then added in one portion at RT, and the resulting mixture stirred at 70° C. for 2.5 h. The reaction mixture was cooled to RT, quenched with aqueous HCl (1 M), and extracted with EtOAc. The layers were separated, the organic layer washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was absorbed onto silica gel and purified by flash chromatography (ethyl acetate/hexane, gradient from 5:95 to 25:75) to afford a mixture of 1-(2-methyl-sulfanyl-pyrimidin-4-yl)-H-indazole and 2-(2-methylsulfanyl-pyrimidin-4-yl)-2H-indazole (3.77 g, 78% yield) as a beige solid.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. customquenched with aqueous HCl (1 M)
  3. extractionextracted with EtOAc
  4. customThe layers were separated
  5. washthe organic layer washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was absorbed onto silica gel
  10. custompurified by flash chromatography (ethyl acetate/hexane, gradient from 5:95 to 25:75)
  11. customto afford

Sources & evidence

ORD record
ord-d3f13262ba52444089402b0f4f7feb56
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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