Hydrochloric Acid → 4'-({4-[4-Hydroxymethylbenzyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile

HRID 1688419Notes

Reaction equation

HRID 1688419 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2[C:17](=[O:39])[N:18]([CH2:28][C:29]3[CH:38]=[CH:37][C:32]([C:33](OC)=[O:34])=[CH:31][CH:30]=3)[C:19]3[N:20]([N:25]=[CH:26][N:27]=3)[C:21]=2[CH2:22][CH2:23][CH3:24])=[CH:11][CH:10]=1)#[N:2].[OH-].[Na+].O1CCCC1.Cl>CO>[OH:34][CH2:33][C:32]1[CH:31]=[CH:30][C:29]([CH2:28][N:18]2[C:17](=[O:39])[C:16]([CH2:15][C:12]3[CH:13]=[CH:14][C:9]([C:4]4[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=4)=[CH:10][CH:11]=3)=[C:21]([CH2:22][CH2:23][CH3:24])[N:20]3[N:25]=[CH:26][N:27]=[C:19]23)=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 67009166methyl 4-({6-[(2'-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}methyl)benzoate

Product 1

HCID 670093144'-({4-[4-Hydroxymethylbenzyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrileYield 70.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 4-({6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}methyl)benzoate (2.8 g), 1N aqueous sodium hydroxide solution (30 mL), tetrahydrofuran (30 mL) and methanol (30 mL) was stirred at 50° C. for 3 hr. 1 N Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (50 mL), N-methylmorpholine (0.67 mL) and ethyl chlorocarbonate (0.58 mL) was added at 0° C., and the mixture was stirred at the same temperature for 2 hr. The reaction mixture was cooled to −15° C., sodium borohydride (0.57 g) and methanol (10 mL) were added, and the mixture was allowed to gradually warm to room temperature. The reaction mixture was extracted with saturated aqueous ammonium chloride solution and ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.86 g, 70%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe obtained ethyl acetate layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe obtained residue was dissolved in tetrahydrofuran (50 mL)
  6. additionN-methylmorpholine (0.67 mL) and ethyl chlorocarbonate (0.58 mL) was added at 0° C.
  7. stirringthe mixture was stirred at the same temperature for 2 hr
  8. temperatureThe reaction mixture was cooled to −15° C.
  9. additionsodium borohydride (0.57 g) and methanol (10 mL) were added
  10. temperatureto gradually warm to room temperature
  11. extractionThe reaction mixture was extracted with saturated aqueous ammonium chloride solution and ethyl acetate
  12. washThe ethyl acetate layer was washed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customThe solvent was evaporated under reduced pressure
  15. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9ebf2aad1bd342668996a78ffb0ac303
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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