Hydroxylamine → HCID 71598732, compound

HRID 1519735Notes

Reaction equation

HRID 1519735 reaction equation
[NH2:1][OH:2].CO.[CH:5]1([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]#[C:19][C:20]3[CH:25]=[CH:24][C:23]([C:26](=[O:38])[N:27]([CH:29]([C:34]([NH:36][CH3:37])=[O:35])[C:30](OC)=[O:31])[CH3:28])=[CH:22][CH:21]=3)=[CH:12][CH:11]=2)[CH2:7][CH2:6]1.C(OCC)(=O)C>O>[CH:5]1([NH:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13](/[CH:16]=[CH:17]/[C:18]#[C:19][C:20]3[CH:21]=[CH:22][C:23]([C:26]([N:27]([CH3:28])[CH:29]([C:34]([NH:36][CH3:37])=[O:35])[C:30]([NH:1][OH:2])=[O:31])=[O:38])=[CH:24][CH:25]=3)=[CH:14][CH:15]=2)[CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 887MethanolHCID 8857Ethyl AcetateHCID 86679293HCID 86679293, compound

Product 1

HCID 71598732HCID 71598732, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 50% aqueous solution (2.0 mL) of hydroxylamine was added, under ice cooling, to a methanol (4.0 mL) solution of 1-[(cyclopropylamino)methyl]-4-[(1E)-4-(4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}phenyl)but-1-en-3-yn-1-yl]benzene (0.18 g) as obtained in Example 23-(4), and the mixture was stirred for 25 minutes under ice cooling and then stirred for 1.5 hours under water cooling. Ethyl acetate and water were added to the reaction mixture to isolate the organic layer, and the extract was washed with water. The washed extract was dried over anhydrous sodium sulfate, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=50/1→10/1), and further purified by preparative silica gel thin-layer chromatography (chloroform/methanol=10/1) to obtain 2-[({4-[(3E)-4-{4-[(cyclopropylamino)methyl]phenyl}but-3-en-1-yn-1-yl]phenyl}carbonyl)(methyl)amino]-N-hydroxy-N′-methylpropanediamide (Compound 481, light yellow solid) (41 mg, 23%).

Workup

  1. customas obtained in Example 23-(4)
  2. stirringstirred for 1.5 hours under water cooling
  3. customto isolate the organic layer
  4. washthe extract was washed with water
  5. extractionThe washed extract
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. filtrationthe desiccant was filtered out
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=50/1→10/1)
  10. customfurther purified by preparative silica gel thin-layer chromatography (chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-7137edc45ac04696895997217c41d0fb
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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