Methanesulfonic Acid → HCID 68176302, compound

HRID 623834Notes

Reaction equation

HRID 623834 reaction equation
[C:1](=[O:29])([O:24][CH2:25][CH:26]([CH3:28])[CH3:27])[O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([NH:22][NH2:23])=[O:21])[N:14]=2)[CH:4]=1.[CH3:30]OC(OC)OC.CS(O)(=O)=O.CO.ClCCl>C1COCC1>[C:1](=[O:29])([O:24][CH2:25][CH:26]([CH3:27])[CH3:28])[O:2][C:3]1[CH:8]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:6]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]3[O:21][CH:30]=[N:23][N:22]=3)[N:14]=2)[CH:4]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 21226129Dichloromethane methanolHCID 68176300HCID 68176300, compound

Product 1

HCID 68176302HCID 68176302, compoundYield 4.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

In a 100-mL, 3-neck round-bottomed flask equipped with nitrogen inlet, and a rubber septum, (Z)-3-(1-(3-hydrazinyl-3-oxoprop-1-enyl)-1H-1,2,4-triazol-3-yl)-5-(trifluoromethyl)phenyl isobutyl carbonate (2 g, 1.0 eq.) was dissolved in THF (20 mL, 10V). Trimethylorthoformate (0.56 g, 1.1 eq.) and methanesulphonic acid (0.23 g, 0.5 eq.) were added and the reaction was refluxed at 70° C. for 2-3 h. The progress of the reaction was followed by TLC analysis on silica gel with 10% MeOH-dichloromethane as mobile phase. SM Rf=0.40 and Product Rf=0.5. Reaction mixture was poured into ice water (100 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine solution (3×50 mL), dried over MgSO4, filtered, and concentrated by rotary evaporation (25° C., 20 mmHg) to afford 2.5 g of crude compound. The crude reaction mixture was purified by column chromatography using silica 60/120 using dichloromethane:Methanol as mobile phase. The column was packed in dichloromethane and started eluting in dichloromethane in gradient manner starting with fraction collection (25-mL fractions). Compound started eluting with 0.8% Methanol in dichloromethane. Fractions containing such TLC profile was collected together to obtain pure compound (0.1 g).

Workup

  1. customIn a 100-mL, 3-neck round-bottomed flask equipped with nitrogen inlet
  2. customReaction mixture
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic layers were washed with brine solution (3×50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation (25° C., 20 mmHg)
  8. customto afford 2.5 g of crude compound
  9. customThe crude reaction mixture
  10. customwas purified by column chromatography
  11. washstarted eluting in dichloromethane in gradient manner
  12. customstarting with fraction collection (25-mL fractions)
  13. washCompound started eluting with 0.8% Methanol in dichloromethane
  14. additionFractions containing such TLC profile
  15. customwas collected together

Sources & evidence

ORD record
ord-544af5e0f8f4444e941bdb0cfae88aea
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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