Hydroxylamine HCl → HCID 178438445, compound

HRID 2062969Notes

Reaction equation

HRID 2062969 reaction equation
[Cl-].O[NH3+].[C:4](=[O:7])([O-])[OH:5].[Na+].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([C@H:19]2[CH2:24][CH2:23][C@H:22]([N:25]3[C:30](=[O:31])[C:29]([CH2:32][C:33]4[CH:38]=[CH:37][C:36]([C:39]5[C:40]([C:45]#[N:46])=[CH:41][CH:42]=[CH:43][CH:44]=5)=[CH:35][CH:34]=4)=[C:28]([CH2:47][CH2:48][CH3:49])[N:27]4[N:50]=[CH:51][N:52]=[C:26]34)[CH2:21][CH2:20]2)=[O:18])=[CH:13][CH:12]=1.[N:53]12CCCN=C1CCCCC2>C(OCC)(=O)C.O1CCCC1.CS(C)=O>[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]([C@H:19]2[CH2:20][CH2:21][C@H:22]([N:25]3[C:30](=[O:31])[C:29]([CH2:32][C:33]4[CH:38]=[CH:37][C:36]([C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=5[C:45]5[NH:53][C:4](=[O:7])[O:5][N:46]=5)=[CH:35][CH:34]=4)=[C:28]([CH2:47][CH2:48][CH3:49])[N:27]4[N:50]=[CH:51][N:52]=[C:26]34)[CH2:23][CH2:24]2)=[O:18])=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 21645Hydroxylamine HClHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 178438569HCID 178438569, compound

Product 1

HCID 178438445HCID 178438445, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.88 g), sodium hydrogen carbonate (1.4 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-[(4-{trans-4-[(4-methoxyphenyl)carbonyl]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.5 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then 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 tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.16 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.14 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. 25% Sulfuric acid (5 mL) and ethanol (15 mL) were added to the obtained residue, and the mixture was stirred at 100° C. for 16 hr. The precipitated solid was collected by filtration to give the title compound as a colorless amorphous solid (0.24 g, 44%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. washwashed with water
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue obtained by silica gel column chromatography
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. washwashed with saturated aqueous potassium hydrogensulfate solution
  8. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. addition25% Sulfuric acid (5 mL) and ethanol (15 mL) were added to the obtained residue
  11. stirringthe mixture was stirred at 100° C. for 16 hr
  12. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-5f74777c248847929a90632c12e7d99f
Source dataset
uspto-grants-2012_10
Patent number
US08283353B2

Reaction notes

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