Methanesulfonic Acid → HCID 57524425, compound

HRID 623821Notes

Reaction equation

HRID 623821 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]=[CH:11][N:10](/[CH:13]=[CH:14]\[C:15]([NH:17][NH2:18])=[O:16])[N:9]=2)[CH:5]=[C:4]([O:19][CH:20]([CH3:22])[CH3:21])[N:3]=1.[CH3:23]OC(OC)OC.CS(O)(=O)=O.CO.ClCCl>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]=[CH:11][N:10](/[CH:13]=[CH:14]\[C:15]3[O:16][CH:23]=[N:18][N:17]=3)[N:9]=2)[CH:5]=[C:4]([O:19][CH:20]([CH3:22])[CH3:21])[N:3]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 21226129Dichloromethane methanolHCID 86672065HCID 86672065, compound

Product 1

HCID 57524425HCID 57524425, compoundYield 2.3%

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-(3-(2-chloro-6-isopropoxypyridin-4-yl)-1H-1,2,4-triazol-1-yl)acrylohydrazide (1.11 gm, 1.0 eq.) was dissolved in THF (17 mL, 15V). Trimethylorthoformate (0.364 g, 1.1 eq.) was added followed by methane sulphonic acid (0.178 g, 0.5 eq.). The Reaction mixture was refluxed at 70° C. for 2 h. The progress of the reaction was followed by TLC analysis on silica gel with 10% MeOH-dichloromethane as mobile phase. Reaction mixture was poured in to ice water (500 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine solution (3×15 mL), dried over NaSO4, filtered, and concentrated by rotary evaporation (25° C., 20 mmHg) to afford 1 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 fraction each) from 35-40% ethyl acetate in hexane. Compound started eluting with 35% ethylacetate in hexane. Fraction containing such TLC profile was collected together to obtain pure compound (26 mg), Yield: 0.026 g (2.6%), 1H NMR: (400 MHz, DMSO) δ =10.25 (s, 1H), 8.50 (s, 1H), 7.608-7.610 (d, 1H), 7.524-7.496 (s, J=11.2, 1H), 6.359-6.360 (d, 1H), 6.316-7.288 (s, J=11.2, 1H), 5.385-5.323 (m, 1H), 1.42-1.38 (s, 6H). LC-MS: Calculated for C15H14ClN5O2(M+H)+332.75 Found: 332.8 at 3.354 min (93.31%).

Workup

  1. customIn a 100 mL, 3-neck round-bottomed flask equipped with nitrogen inlet
  2. customReaction mixture
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic layers were washed with brine solution (3×15 mL)
  5. dry with materialdried over NaSO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation (25° C., 20 mmHg)
  8. customto afford 1 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 fraction each) from 35-40% 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-ae4dbe82ae25497aa78afc8c7549f54e
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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