Hydrochloric Acid → 4'-{[4-(2,3-Dimethyl-1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-4-fluorobiphenyl-2-carbonitrile

HRID 2048369Notes

Reaction equation

HRID 2048369 reaction equation
O1C2(C[CH2:9][CH:8]([N:11]3[C:16](=[O:17])[C:15]([CH2:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]5[C:26]([C:32]#[N:33])=[CH:27][C:28]([F:31])=[CH:29][CH:30]=5)=[CH:21][CH:20]=4)=[C:14]([CH2:34][CH2:35][CH3:36])[N:13]4[N:37]=[C:38]([CH3:40])[N:39]=[C:12]34)[CH2:7][CH2:6]2)OCC1.Cl.O1CC[CH2:44][CH2:43]1.[C:47]([O:50][CH2:51][CH3:52])(=[O:49])[CH3:48]>>[CH3:52][CH:51]1[CH:43]([CH3:44])[O:49][C:47]2([CH2:6][CH2:7][CH:8]([N:11]3[C:16](=[O:17])[C:15]([CH2:18][C:19]4[CH:20]=[CH:21][C:22]([C:25]5[C:26]([C:32]#[N:33])=[CH:27][C:28]([F:31])=[CH:29][CH:30]=5)=[CH:23][CH:24]=4)=[C:14]([CH2:34][CH2:35][CH3:36])[N:13]4[N:37]=[C:38]([CH3:40])[N:39]=[C:12]34)[CH2:9][CH2:48]2)[O:50]1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 670100244'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-4-fluorobiphenyl-2-carbonitrile

Product 1

HCID 670096714'-{[4-(2,3-Dimethyl-1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-4-fluorobiphenyl-2-carbonitrileYield 100%

Conditions

Temperature
70 °C

Procedure

A mixture of 4′-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-4-fluorobiphenyl-2-carbonitrile (1.1 g), 3N hydrochloric acid (30 mL) and tetrahydrofuran (30 mL) was stirred at 70° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in toluene (30 mL), 2,3-dimethylpropane-1,3-diol (0.2 g) and p-toluenesulfonic acid monohydrate (0.004 g) were added, and the mixture was subjected to an azeotropic dehydration reaction by stirring at 110° C. for 3 hr in a reaction vessel equipped with a Dean-stark trap. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.3 g, 100%).

Workup

  1. washwashed with saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionThe obtained residue was dissolved in toluene (30 mL)
  5. addition2,3-dimethylpropane-1,3-diol (0.2 g) and p-toluenesulfonic acid monohydrate (0.004 g) were added
  6. customthe mixture was subjected to an azeotropic dehydration reaction
  7. stirringby stirring at 110° C. for 3 hr in a reaction vessel
  8. customequipped with a Dean-stark trap
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-84ce77272c7e4554935c008f79981213
Source dataset
uspto-grants-2013_11
Patent number
US08592431B2

Reaction notes

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