Methanol → HCID 57524427, compound

HRID 623828Notes

Reaction equation

HRID 623828 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:15]2[N:19]=[CH:18][N:17](/[CH:20]=[CH:21]\[C:22]([NH:24][NH2:25])=[O:23])[N:16]=2)[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)(=[O:4])=[O:3].[CH3:26]OC(OC)OC.CS(O)(=O)=O.CO>O.ClCCl>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:15]2[N:19]=[CH:18][N:17](/[CH:20]=[CH:21]\[C:22]3[O:23][CH:26]=[N:25][N:24]=3)[N:16]=2)[CH:8]=[C:9]([C:11]([F:12])([F:14])[F:13])[CH:10]=1)(=[O:4])=[O:3]

Participants

7

Reactant 4

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 70564058HCID 70564058, compound

Product 1

HCID 57524427HCID 57524427, compoundYield 19.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 3-neck 25 mL round-bottomed flask, (Z)-3-(3-(3-(methylsulfonyl)-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylohydrazide (0.300 g, 1.0 eq.) under N2 atmosphere was added trimethylorthoformate (0.26 g, 3.0 eq.) and Methane sulphonic acid (0.027 g, 0.1 eq.). Reaction mixture was refluxed at 80° C. for 1 h. 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=0.25 and Product Rf=0.41. The resulting yellow reaction mass was poured in 30 mL water and extracted with 3×20 mL ethylacetate. Organic layer was washed with brine solution followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 0.250 g of crude compound. The crude reaction mixture was purified by column chromatography using silica 60/120 using methanol: dichloromethane as mobile phase. The column (2×10 cm) was packed in dichloromethane and started eluting in Methanol in gradient manner starting with fraction collection (25-mL fractions) from 1.5% to 2.5% methanol in dichloromethane. Compound started eluting with 1.5% methanol in dichloromethane. Fraction containing such TLC profile was collected together to obtain pure compound (0.060 g), Yield (20%) 1H NMR (400 MHz, CDCl3) δ 9.76 (S, 1H), 7.2-8.6 (m, 7H), 7.39-7.41 (d, J=10.8, 1H), 5.58-5.88 (d, J=11.2 Hz, 1H), 5.39 (S, 2H), 4.70-4.73 (m, 1H), 1.39-1.41 (d, 6H): LCMS for C21H19F3N4O3 [M+1]+ 432.4 found 432.96 at RT 4.217 min.

Workup

  1. customReaction mixture
  2. extractionextracted with 3×20 mL ethylacetate
  3. washOrganic layer was washed with brine solution
  4. customby drying
  5. concentrationOrganic layer was concentrated under reduced pressure
  6. customto afford 0.250 g of crude compound
  7. customThe crude reaction mixture
  8. customwas purified by column chromatography
  9. washstarted eluting in Methanol in gradient manner
  10. customstarting with fraction collection (25-mL fractions) from 1.5% to 2.5% methanol in dichloromethane
  11. washCompound started eluting with 1.5% methanol in dichloromethane
  12. additionFraction containing such TLC profile
  13. customwas collected together

Sources & evidence

ORD record
ord-aebb476ae16d4b3583fc1ec6596c84fa
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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