Methanesulfonic Acid → 5-[4-(2-Trifluoromethylbenzoyl)piperazin-1-YL]-[1,3,4]thiadiazole-2-carboxylic acid ethyl ester

HRID 2074128Notes

Reaction equation

HRID 2074128 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[C:5](=O)[NH:6][NH:7][C:8]([N:10]1[CH2:15][CH2:14][N:13]([C:16](=[O:27])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]([F:26])([F:25])[F:24])[CH2:12][CH2:11]1)=[S:9])[CH3:2].CS(O)(=O)=O>C1(C)C=CC=CC=1.CN1CCCC1=O>[CH2:1]([O:3][C:4]([C:5]1[S:9][C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16](=[O:27])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]([F:26])([F:25])[F:24])[CH2:12][CH2:11]2)=[N:7][N:6]=1)=[O:29])[CH3:2]

Participants

5

Reactant 2

HCID 6395Methanesulfonic AcidHCID 86620011HCID 86620011, compound

Product 1

HCID 115823885-[4-(2-Trifluoromethylbenzoyl)piperazin-1-YL]-[1,3,4]thiadiazole-2-carboxylic acid ethyl esterYield 68%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Oxo-{N′-[4-(2-trifluoromethylbenzoyl)piperazine-1-carbothioyl]hydrazino}-acetic acid ethyl ester (2.88 g, 6.56 mmol) was dissolved in a mixture of 50 mL of toluene and 10 mL of N-methyl-2-pyrrolidone. Methanesulfonic acid (0.723 mL, 11.15 mmol) was then added dropwise over 5 minutes to the stirred solution. The mixture was refluxed for 1.5 hours, then evaporated to 10 mL, and then 20 mL of water was added. The pH of the solution was adjusted to 8 by saturated NaHCO3. The mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography to give the title compound in 68% yield (1.84 g). 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J=7.8 Hz, 1H), 7.64 (dd, J=7.5, 7.5 Hz, 1H), 7.60 (dd, J=7.5, 7.5 Hz, 1H), 7.35 (d, J=7.3 Hz, 1H), 4.44 (q, J=7.1 Hz, 2H), 4.06-4.11 (m, 1H), 3.86-3.91 (m, 1H), 3.56-3.77 (m, 4H), 3.35 (t, J=5.4 Hz, 2H), 1.41 (t, J=7.1 Hz, 3H). MS (ES+) m/z 415.5 (M+1).

Workup

  1. temperatureThe mixture was refluxed for 1.5 hours
  2. customevaporated to 10 mL
  3. addition20 mL of water was added
  4. extractionThe mixture was extracted with ethyl acetate (2×50 mL)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0268fa210a4e4783b8a6699b93197fda
Source dataset
uspto-grants-2011_04
Patent number
US07919496B2

Reaction notes

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