Methanesulfonic Acid → HCID 57524026, compound

HRID 623807Notes

Reaction equation

HRID 623807 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[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:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:24]OC(OC)OC.CS(O)(=O)=O.CCOC(C)=O.CCCCCC>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]3[O:21][CH:24]=[N:23][N:22]=3)[N:14]=2)[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 21226206Ethyl acetate hexaneHCID 70563549HCID 70563549, compound

Product 1

HCID 57524026HCID 57524026, compoundYield 10.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

In a 50-mL, 3N round-bottomed flask equipped with nitrogen inlet, and a rubber septum, (Z)-3-(3-(3-methoxy-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylohydrazide (0.920 g, 1.0 eq.) was dissolved in THF (23 mL, 25V), added trimethylorthoformate (0.328 g, 1.1 eq.) and added methanesulphonic acid (0.161 g, 0.5 eq.). The Reaction mixture was refluxed at 70° C. for 2-3 h. The progress of the reaction was followed by TLC analysis on silica gel with 50% EtOAc-hexane as mobile phase. SM Rf=0.40 and Product Rf=0.5. Reaction mixture was poured into ice water (50 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 0.60 g of crude compound. The crude reaction mixture was purified by column chromatography using silica 60/120 using ethyl acetate:hexane as mobile phase. The column (5×10 cm) was packed in hexane and started eluting in ethyl acetate in gradient manner starting with fraction collection (25-mL fractions) from 35% to 40% ethyl acetate in hexane. Compound started eluting with 35% ethylacetate in hexane. Fraction containing such TLC profile was collected together to obtain pure compound (100 mg), Yield (10.54). 1H NMR (400 MHz, CDCl3) δ 10.25 (S, 1H), 8.5 (S, 1H), 8.04 (S, 1H), 7.89 (S, 1H), 7.51-7.54 (d, J=11.2 Hz, 1H), 7.28 (S, 1H), 7.23 (S, 1H), 6.27-6.30 (d, J=10.8 Hz, 1H), 3.35 (S, 3H): LCMS for C14H10F3N5O2 [M+1]+ 337.3 at 3.60 min (LCMS 93.43%).

Workup

  1. customIn a 50-mL, 3N 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 0.60 g of crude compound
  9. customThe crude reaction mixture
  10. customwas purified by column chromatography
  11. washstarted eluting in ethyl acetate in gradient manner
  12. customstarting with fraction collection (25-mL fractions) from 35% to 40% ethyl acetate in hexane
  13. washCompound started eluting with 35% ethylacetate in hexane
  14. additionFraction containing such TLC profile
  15. customwas collected together

Sources & evidence

ORD record
ord-313494ce15ee4f2d9296709c8e9436a5
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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