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

HRID 519535Notes

Reaction equation

HRID 519535 reaction equation
O1[C:5]2([CH2:10][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:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=5)=[CH:21][CH:20]=4)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]4[N:36]=[CH:37][N:38]=[C:12]34)[CH2:7][CH2:6]2)[O:4][CH2:3]C1.Cl.CI.[H-].[Na+]>C(OCC)(=O)C.CN(C)C=O.O1CCCC1>[CH3:3][O:4][CH:5]1[CH2:6][CH2:7][CH:8]([N:11]2[C:16](=[O:17])[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=4)=[CH:21][CH:20]=3)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]3[N:36]=[CH:37][N:38]=[C:12]23)[CH2:9][CH2:10]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 670088084'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 670095774'-{[4-(4-Methoxycyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrileYield 28%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of 4′-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (2 g), 6N hydrochloric acid (20 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 methanol (30 mL), sodium borohydride (0.18 g) was added, and the mixture was stirred at room temperature for 1 hr. After evaporation of the solvent under reduced pressure, the residue was extracted with water and 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 residue obtained by silica gel column chromatography was dissolved in N,N-dimethylformamide (10 mL), methyl iodide (0.13 mL) and sodium hydride (0.05 g) were added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogensulfate solution and then 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 to give the title compound as a colorless solid (0.21 g, 28%).

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 methanol (30 mL)
  5. additionsodium borohydride (0.18 g) was added
  6. stirringthe mixture was stirred at room temperature for 1 hr
  7. customAfter evaporation of the solvent under reduced pressure
  8. extractionthe residue was extracted with water and ethyl acetate
  9. washThe obtained ethyl acetate layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customThe residue obtained by silica gel column chromatography
  13. stirringthe mixture was stirred at room temperature for 16 hr
  14. washwashed with 5% aqueous potassium hydrogensulfate solution
  15. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  16. customThe solvent was evaporated under reduced pressure
  17. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9e6b32a02b6d4d439fbabfd01f574885
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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