Hydroxylamine HCl → HCID 136063731, compound

HRID 520153Notes

Reaction equation

HRID 520153 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].[OH:9][C:10]([CH:13]1[CH2:18][CH2:17][CH:16]([N:19]2[C:24](=[O:25])[C:23]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[C:34]([C:39]#[N:40])=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:29][CH:28]=3)=[C:22]([CH2:41][CH2:42][CH3:43])[N:21]3[N:44]=[CH:45][N:46]=[C:20]23)[CH2:15][CH2:14]1)([CH3:12])[CH3:11]>CS(C)=O.C(OCC)(=O)C>[OH:9][C:10]([CH:13]1[CH2:18][CH2:17][CH:16]([N:19]2[C:24](=[O:25])[C:23]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[C:39]4[NH:3][C:4](=[O:7])[O:5][N:40]=4)=[CH:29][CH:28]=3)=[C:22]([CH2:41][CH2:42][CH3:43])[N:21]3[N:44]=[CH:45][N:46]=[C:20]23)[CH2:15][CH2:14]1)([CH3:12])[CH3:11]

Participants

6

Reactant 3

HCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 67009717HCID 67009717, compound

Product 1

HCID 136063731HCID 136063731, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of hydroxylammonium chloride (208 mg), sodium hydrogen carbonate (336 mg) and dimethyl sulfoxide (3 mL) was stirred at 60° C. for 30 min, a solution of 4′-({4-[4-(1-hydroxy-1-methylethyl)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (100 mg) in dimethyl sulfoxide (1 mL) 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, and the residue was dissolved in tetrahydrofuran (8 mL). N,N′-Carbonyldiimidazole (39 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (37 mg) 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, and the residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=65/35→35/65 (volume ratio)] to give the title compound as a colorless amorphous compound (37 mg, 33%).

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. dissolutionthe residue was dissolved in tetrahydrofuran (8 mL)
  6. additionN,N′-Carbonyldiimidazole (39 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (37 mg) were added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. additionThe reaction mixture was diluted with ethyl acetate
  9. washwashed with saturated aqueous potassium hydrogensulfate solution
  10. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=65/35→35/65 (volume ratio)]

Sources & evidence

ORD record
ord-f15e86b181e44a26a7d08540279d9745
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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