p-Toluenesulfonic acid → 6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl-4-(tetrahydrospiro[cyclohexane-1,2'-furo[3,4-d][1,3]dioxol]-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

HRID 2048851Notes

Reaction equation

HRID 2048851 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C:13](=[O:14])[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[C:28]4[NH:32][C:31](=[O:33])[O:30][N:29]=4)=[CH:18][CH:17]=3)=[C:11]([CH2:34][CH2:35][CH3:36])[N:10]3[N:37]=[CH:38][N:39]=[C:9]23)[CH2:4][CH2:3]1.[O:40]1[CH2:44][CH:43](O)[CH:42]([OH:46])[CH2:41]1.CC1C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[O:33]=[C:31]1[O:30][N:29]=[C:28]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[C:19]2[CH:18]=[CH:17][C:16]([CH2:15][C:12]3[C:13](=[O:14])[N:8]([CH:5]4[CH2:6][CH2:7][C:2]5([O:46][CH:42]6[CH2:41][O:40][CH2:44][CH:43]6[O:1]5)[CH2:3][CH2:4]4)[C:9]4[N:10]([N:37]=[CH:38][N:39]=4)[C:11]=3[CH2:34][CH2:35][CH3:36])=[CH:21][CH:20]=2)[NH:32]1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 908031,4-AnhydrothreitolHCID 516892Sodium BicarbonateHCID 1360639444-(4-oxocyclohexyl)-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

Product 1

HCID 1363371486-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl-4-(tetrahydrospiro[cyclohexane-1,2'-furo[3,4-d][1,3]dioxol]-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-oneYield 68%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 4-(4-oxocyclohexyl)-6-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one (0.30 g), tetrahydrofuran-3,4-diol (0.11 g), 4-methylbenzenesulfonic acid (0.011 g) and toluene (20 mL) was heated under reflux for 6 hr using a Dean-Stark trap. The reaction mixture was added to saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography and recrystallized (ethyl acetate-hexane) to give the title compound as a colorless solid (0.23 g, 68%).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 6 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography
  8. customrecrystallized (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-ad81f9e8c5d64eb9b1a7cefb19e1415a
Source dataset
uspto-grants-2013_11
Patent number
US08592431B2

Reaction notes

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