Hydrochloric Acid → HCID 178438769, compound

HRID 519858Notes

Reaction equation

HRID 519858 reaction equation
[O:1]1[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)=[C:21]([O:33][CH3:34])[CH:20]=4)=[C:14]([CH2:35][CH2:36][CH3:37])[N:13]4[N:38]=[CH:39][CH:40]=[C:12]34)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.Cl.[OH-:42].[Na+].O1CC[CH2:46][CH2:45]1>C(OCC)(=O)C>[C:31]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C:22]1[CH:23]=[CH:24][C:19]([CH2:18][C:15]2[C:16](=[O:17])[N:11]([C@H:8]3[CH2:7][CH2:6][C@H:5]([O:4][CH2:3][C:2]([O:1][CH2:45][CH3:46])=[O:42])[CH2:10][CH2:9]3)[C:12]3[N:13]([N:38]=[CH:39][CH:40]=3)[C:14]=2[CH2:35][CH2:36][CH3:37])=[CH:20][C:21]=1[O:33][CH3:34])#[N:32]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 670098494'-{[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl]methyl}-2'-methoxybiphenyl-2-carbonitrile

Product 1

HCID 178438769HCID 178438769, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 4′-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl]methyl}-2′-methoxybiphenyl-2-carbonitrile (0.25 g) in tetrahydrofuran (3 mL) was added 3M hydrochloric acid (3 mL), and the mixture was stirred at 60° C. for 12 hr. The mixture was allowed to cool, and diluted with ethyl acetate, and the mixture was neutralized with 1 M aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in ethanol (3 mL)-tetrahydrofuran (3 mL). Thereto was added sodium borohydride (0.019 g) at 0° C. After stirring for 1 hr, ethyl acetate and saturated aqueous ammonium chloride solution were added. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in methylene chloride (2 mL), rhodium acetate (dimer, 0.020 g) and then ethyl diazoacetate (0.86 mL) were added dropwise, and the mixture was stirred for 3 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 water and then with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.13 g, 53%).

Workup

  1. temperatureto cool
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in ethanol (3 mL)-tetrahydrofuran (3 mL)
  7. additionThereto was added sodium borohydride (0.019 g) at 0° C
  8. stirringAfter stirring for 1 hr
  9. additionethyl acetate and saturated aqueous ammonium chloride solution were added
  10. extractionThe mixture was extracted with ethyl acetate
  11. washthe organic layer was washed with water and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated
  14. dissolutionThe residue was dissolved in methylene chloride (2 mL)
  15. additionrhodium acetate (dimer, 0.020 g) and then ethyl diazoacetate (0.86 mL) were added dropwise
  16. stirringthe mixture was stirred for 3 hr
  17. additionEthyl acetate and water were added to the reaction mixture
  18. extractionthe mixture was extracted with ethyl acetate
  19. washThe organic layer was washed with water
  20. dry with materialwith saturated brine, dried over anhydrous magnesium sulfate
  21. concentrationconcentrated
  22. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6dc7fdb9a39245d68db1e403589f7c23
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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