Methanesulfonic Acid → HCID 57524353, compound

HRID 623803Notes

Reaction equation

HRID 623803 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[CH:15][N:14](/[CH:17]=[CH:18]\[C:19]([NH:21][NH2:22])=[O:20])[N:13]=2)[CH:5]=[C:6]([O:8][CH:9]([CH3:11])[CH3:10])[CH:7]=1.[CH3:23]OC(OC)OC.CS(O)(=O)=O.CCOC(C)=O.CCCCCC>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[CH:15][N:14](/[CH:17]=[CH:18]\[C:19]3[O:20][CH:23]=[N:22][N:21]=3)[N:13]=2)[CH:5]=[C:6]([O:8][CH:9]([CH3:11])[CH3:10])[CH:7]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 21226206Ethyl acetate hexaneHCID 70565584HCID 70565584, compound

Product 1

HCID 57524353HCID 57524353, compoundYield 1,050.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

In a 25-mL, 3N round-bottomed flask equipped with nitrogen inlet, and a rubber septum, (Z)-3-(3-(3-chloro-5-isopropoxyphenyl)-1H-1,2,4-triazol-1-yl)acrylohydrazide (0.3 g, 1.0 eq.) was dissolved in THF (7.5 mL, 25V) and trimethylorthoformate (0.109 g, 1.1 eq) and added Methanesulphonic acid (0.053 g, 0.5 eq) was added into it. 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 (10 mL) slurry and compound was extracted with EtOAc (3×15 mL). The combined organic layers was washed with brine solution (3×15 mL), dried over MgSO4, filtered, and concentrated by rotary evaporation (25° C., 20 mmHg) to afford 0.28 g of Crude compound. evaporation (25° C., 20 mmHg) to afford 3.25 g of a yellow oil. The resulting crude compound was subjected to column purification. 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 (50 mg), Yield (16.18%). 1H NMR (400 MHz, CDCl3) δ 10.3 (s, 1H), 8.50 (s, 1H), 8.46 (s, 1H), 7.74 (s, 1H), 7.63 (s, 1H) 7.50-7.53 (d, J=12 Hz, 1H) 7.01 (s, 1H) 6.27-6.30 (d, J=12 Hz, 1H) 4.65-4.71 (m, 1H) 1.39-1.40 (d, J=4 Hz, 6H) LCMS C11H7ClF3N3 (331.76)[M+1] found 331.85 at 3.910. (LCMS 99.67%).

Workup

  1. customIn a 25-mL, 3N round-bottomed flask equipped with nitrogen inlet
  2. additionwas added into it
  3. customReaction mixture
  4. extractionwas extracted with EtOAc (3×15 mL)
  5. washThe combined organic layers was washed with brine solution (3×15 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation (25° C., 20 mmHg)
  9. customto afford 0.28 g of Crude compound
  10. customevaporation (25° C., 20 mmHg)

Sources & evidence

ORD record
ord-000f979806da48029c477dd9c62b43ab
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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