Hydrochloric Acid → HCID 178438457, compound

HRID 520099Notes

Reaction equation

HRID 520099 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:13](=[O:14])[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=4)=[CH:18][CH:17]=3)=[C:11]([CH2:30][CH2:31][CH3:32])[N:10]3[N:33]=[CH:34][N:35]=[C:9]23)[CH2:4][CH2:3]1.[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41](O)=[CH:40][CH:39]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=[N:65][C:66]([O:68]C(C)C)=[O:67].Cl.[Cl-].O[NH3+].C(=O)([O-])O.[Na+]>O1CCCC1.O.C(OCC)(=O)C.CS(C)=O>[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41]([O:1][C@@H:2]2[CH2:7][CH2:6][C@H:5]([N:8]3[C:13](=[O:14])[C:12]([CH2:15][C:16]4[CH:21]=[CH:20][C:19]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=5[C:28]5[NH:65][C:66](=[O:67])[O:68][N:29]=5)=[CH:18][CH:17]=4)=[C:11]([CH2:30][CH2:31][CH3:32])[N:10]4[N:33]=[CH:34][N:35]=[C:9]34)[CH2:4][CH2:3]2)=[CH:40][CH:39]=1

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 90154-MethoxyphenolHCID 11776TriphenylphosphineHCID 21645Hydroxylamine HClHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 516892Sodium BicarbonateHCID 178438592HCID 178438592, compound

Product 1

HCID 178438457HCID 178438457, compoundYield 39%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4′-{[4-(trans-4-hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.46 g), 4-methoxyphenol (0.27 g) and triphenylphosphine (0.28 g) in tetrahydrofuran (1.0 mL) was added dropwise a solution of diisopropyl azodicarboxylate (0.58 mL, 1.9 M toluene solution) in tetrahydrofuran (1.5 mL) at 0° C., and the mixture was stirred at room temperature for 5.5 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. A solution of the residue obtained by purification by silica gel column chromatography in dimethyl sulfoxide (2 mL) was added to a mixture of hydroxylammonium chloride (1.0 g), sodium hydrogen carbonate (1.7 g), and dimethyl sulfoxide (3 mL), which had been stirred at 40° C. for 30 min in advance, and the mixture was stirred at 90° C. for 15 hr. Ethyl acetate and water were added to the reaction mixture, 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 dissolved in tetrahydrofuran (5 mL). N,N′-Carbonyldiimidazole (0.19 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.18 mL) were added, and the mixture was stirred at room temperature for 40 min. Ethyl acetate and water were added to the reaction mixture, and the mixture was acidified with 1 M hydrochloric acid and 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 to give the title compound as a colorless solid (0.25 g, 39%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customA solution of the residue obtained by purification by silica gel column chromatography in dimethyl sulfoxide (2 mL)
  6. stirringhad been stirred at 40° C. for 30 min in advance
  7. stirringthe mixture was stirred at 90° C. for 15 hr
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. dissolutionthe residue was dissolved in tetrahydrofuran (5 mL)
  13. additionN,N′-Carbonyldiimidazole (0.19 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.18 mL) were added
  14. stirringthe mixture was stirred at room temperature for 40 min
  15. additionEthyl acetate and water were added to the reaction mixture
  16. extractionextracted with ethyl acetate
  17. washThe organic layer was washed with saturated brine
  18. dry with materialdried over anhydrous magnesium sulfate
  19. customThe solvent was evaporated under reduced pressure
  20. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3f3c12b51b3943539741f429e960fb1e
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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