p-Toluenesulfonic acid → 1-{[2-(Methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-one

HRID 1851713Notes

Reaction equation

HRID 1851713 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[S:8][C:7]2=[N:9][C:10]([C:14]([F:17])([F:16])[F:15])=[C:11]([CH2:12]O)[N:6]2[N:5]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:29][C:30]([F:40])([F:39])[CH2:31][CH2:32][CH:33]1[CH2:37][NH:36][C:35](=[O:38])[NH:34]1>C1(C)C=CC=CC=1>[CH3:1][O:2][CH2:3][C:4]1[S:8][C:7]2=[N:9][C:10]([C:14]([F:17])([F:16])[F:15])=[C:11]([CH2:12][N:36]3[CH2:37][CH:33]([CH2:32][CH2:31][C:30]([F:39])([F:40])[F:29])[NH:34][C:35]3=[O:38])[N:6]2[N:5]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 70976689HCID 70976689, compoundHCID 86720187HCID 86720187, compound

Product 1

HCID 665716681-{[2-(Methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-oneYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methanol a3 (3.26 g, 0.122 mol, 1 eq) and p-toluenesulphonic acid (2.10 g, 0.122 mol, 1 eq) are successively added to a solution of 4-(3,3,3-trifluoropropyl)imidazolidin-2-one a10 (2.22 g, 0.122 mol, 1 eq) in toluene (450 ml). The mixture is heated at 110° C. overnight. The reaction is not complete and another portion of intermediate a10 (1 g, 5.49 mmol, 0.45 eq) is added. The mixture is heated at 110° C. overnight, then the solvent is evaporated under reduced pressure. Water is added to the residue, the mixture is extracted with CH2Cl2, the organic layer is dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by chromatography over silicagel (eluent: CH2Cl2/MeOH/NH4OH 98/2/0.2) to afford 336 mg of 1-{[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)imidazolidin-2-one 5 as a yellow oil.

Workup

  1. additionanother portion of intermediate a10 (1 g, 5.49 mmol, 0.45 eq) is added
  2. temperatureThe mixture is heated at 110° C. overnight
  3. customthe solvent is evaporated under reduced pressure
  4. additionWater is added to the residue
  5. extractionthe mixture is extracted with CH2Cl2
  6. dry with materialthe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. customcondensed under reduced pressure
  9. customThe residue is purified by chromatography over silicagel (eluent: CH2Cl2/MeOH/NH4OH 98/2/0.2)

Sources & evidence

ORD record
ord-2e15e2b5319e40f59db3ff491547f2be
Source dataset
uspto-grants-2015_02
Patent number
US08957218B2

Reaction notes

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