Formic Acid → HCID 178504657, compound

HRID 623826Notes

Reaction equation

HRID 623826 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1)[C:8](=S)[NH2:9])(=O)=[O:3].[OH2:18].[NH2:19][NH2:20].[CH:21](O)=O.CO>CN(C=O)C.ClCCl>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:8]2[N:9]=[CH:21][NH:20][N:19]=2)[CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1)(=[O:3])=[O:18]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 887MethanolHCID 24654Hydrazine hydrate (1:1)HCID 86672066HCID 86672066, compound

Product 1

HCID 178504657HCID 178504657, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

In a 1-neck 250 mL round-bottomed flask, 3-(methylsulfonyl)-5-(trifluoromethyl)benzothioamide (4.0 g, 1.0 eq.) was dissolved in DMF (40 mL, 10 V) added hydrazine hydrate (1.60 g, 2.0 eq.) and stirred reaction mixture for 3 h. Then formic acid (20 mL, vol) was added and stirred for 1 h at the same temperature. Then temperature increased to 90° C. and maintained for 10-12 hrs. The progress of the reaction was followed by TLC analysis on silica gel with 10% methanol: dichloromethane as mobile phase and visualization with UV, SM Rf=0.30 and Product Rf=0.20. Reaction mixture was quenched into the ice-water slurry (300 mL) and extracted in the ethyl acetate (100 mL×3). Organic layer was washed with sodium bicarbonate solution (100×3 mL) followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 3.0 g of crude compound. The resulting crude compound (4.0 g) was subjected to column purification. The crude reaction mixture was purified by column chromatography using silica 60/120 using methanol: dichloromethane as mobile phase. The column (5×10 cm) was packed in dichloromethane and started eluting in Methanol in gradient manner starting with fraction collection (25 mL fractions) from 3-5% methanol in dichloromethane. Compound started eluting with 3% methanol in dichloromethane. Fraction containing such TLC profile was collected together to obtain pure compound (3.0 g), Yield (73.6%).

Workup

  1. customreaction mixture for 3 h
  2. stirringstirred for 1 h at the same temperature
  3. temperaturemaintained for 10-12 hrs
  4. customReaction mixture
  5. customwas quenched into the ice-water slurry (300 mL)
  6. extractionextracted in the ethyl acetate (100 mL×3)
  7. washOrganic layer was washed with sodium bicarbonate solution (100×3 mL)
  8. customby drying
  9. concentrationOrganic layer was concentrated under reduced pressure
  10. customto afford 3.0 g of crude compound
  11. customThe resulting crude compound (4.0 g) was subjected to column purification
  12. customThe crude reaction mixture
  13. customwas purified by column chromatography
  14. washstarted eluting in Methanol in gradient manner
  15. customstarting with fraction collection (25 mL fractions) from 3-5% methanol in dichloromethane
  16. washCompound started eluting with 3% methanol in dichloromethane
  17. additionFraction containing such TLC profile
  18. customwas collected together

Sources & evidence

ORD record
ord-e1bcd4283bf6426ea44160d092839827
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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