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

HRID 519683Notes

Reaction equation

HRID 519683 reaction equation
[Mg].Cl[CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[O:9]=[C:10]1[C:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[C:24]([C:29]#[N:30])=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:19][CH:18]=2)=[C:14]([CH2:31][CH2:32][CH3:33])[N:13]2[N:34]=[CH:35][N:36]=[C:12]2[N:11]1[CH:37]1[CH2:42][CH2:41][C:40](=[O:43])[CH2:39][CH2:38]1.Cl>BrCCBr.O1CCCC1>[OH:43][C:40]1([CH:3]2[CH2:8][CH2:7][O:6][CH2:5][CH2:4]2)[CH2:41][CH2:42][CH:37]([N:11]2[C:10](=[O:9])[C:15]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]4[C:24]([C:29]#[N:30])=[CH:25][CH:26]=[CH:27][CH:28]=4)=[CH:19][CH:18]=3)=[C:14]([CH2:31][CH2:32][CH3:33])[N:13]3[N:34]=[CH:35][N:36]=[C:12]23)[CH2:38][CH2:39]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1372022H-Pyran, 4-chlorotetrahydro-2×HCID 5462224MagnesiumHCID 670088534'-{[5-Oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 670096254'-({4-[4-hydroxy-4-(tetrahydro-2H-pyran-4-yl)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrileYield 52.5%

Reagents, catalysts & solvents 2

HCID 78391,2-DibromoethaneCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

To a mixture of magnesium (0.10 g) and tetrahydrofuran (1 mL) were added 4-chlorotetrahydro-2H-pyran (0.050 g) and 1,2-dibromoethane (10 drops) under an argon atmosphere. The mixture was heated to initiate the reaction, a solution of 4-chlorotetrahydro-2H-pyran (0.46 g) in tetrahydrofuran (5 mL) was added dropwise at 50° C., and the mixture was stirred at 50° C. for 4 hr. The reaction mixture was cooled to 0° C., a solution of 4′-{[5-oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.50 g) in tetrahydrofuran (5 mL) was added dropwise, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was added to 1 M hydrochloric acid, 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 HPLC to give the title compound as a colorless solid (0.12 g, 20%).

Workup

  1. temperatureThe mixture was heated
  2. customthe reaction
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. stirringthe mixture was stirred at room temperature for 18 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography and HPLC

Sources & evidence

ORD record
ord-b210d217e0a34e79b71a7659289ea32d
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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