Hydroxylamine → HCID 71598731, compound

HRID 1519730Notes

Reaction equation

HRID 1519730 reaction equation
[NH2:1][OH:2].[CH:3]1([NH:6][CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15]/[CH:16]=[CH:17]/[C:18]3[CH:23]=[CH:22][C:21]([C:24](=[O:36])[N:25]([CH:27]([C:32]([NH:34][CH3:35])=[O:33])[C:28](OC)=[O:29])[CH3:26])=[CH:20][CH:19]=3)=[CH:10][CH:9]=2)[CH2:5][CH2:4]1.S([O-])([O-])(=O)=O.[Na+].[Na+]>CO.C(Cl)(Cl)Cl.O.C(OCC)(=O)C>[CH:3]1([NH:6][CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15]/[CH:16]=[CH:17]/[C:18]3[CH:19]=[CH:20][C:21]([C:24]([N:25]([CH3:26])[CH:27]([C:32]([NH:34][CH3:35])=[O:33])[C:28]([NH:1][OH:2])=[O:29])=[O:36])=[CH:22][CH:23]=3)=[CH:10][CH:9]=2)[CH2:5][CH2:4]1

Participants

8

Reactant 3

HCID 787HydroxylamineHCID 24436Sodium SulfateHCID 86679288HCID 86679288, compound

Product 1

HCID 71598731HCID 71598731, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

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-[(3E)-4-(4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}phenyl)but-3-en-1-yn-1-yl]benzene (0.20 g) as obtained in Example 22-(4), and the mixture was stirred for 30 minutes under ice cooling and then stirred for 2 hours under water cooling. Ethyl acetate and water were added to the reaction mixture to isolate the organic layer, and the extract was washed sequentially with water and brine. The precipitate was dissolved with methanol and water, and the organic layer was isolated. Chloroform, methanol and anhydrous sodium sulfate were added to the extract, and the desiccant was filtered out, whereafter the solvents were distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=20/1→10/1), and further purified by preparative silica gel thin-layer chromatography (chloroform/methanol=10/1) to obtain 2-[({4-[(1E)-4-{4-[(cyclopropylamino)methyl]phenyl}but-1-en-3-yn-1-yl]phenyl}carbonyl)(methyl)amino]-N-hydroxy-N′-methylpropanediamide (Compound 477, light yellow solid) (51 mg, 25%).

Workup

  1. customas obtained in Example 22-(4)
  2. stirringstirred for 2 hours under water cooling
  3. customto isolate the organic layer
  4. washthe extract was washed sequentially with water and brine
  5. dissolutionThe precipitate was dissolved with methanol and water
  6. customthe organic layer was isolated
  7. filtrationthe desiccant was filtered out, whereafter the solvents
  8. distillationwere distilled off under reduced pressure
  9. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=20/1→10/1)
  10. customfurther purified by preparative silica gel thin-layer chromatography (chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-f324999ec27d4d2e961634b615765eb6
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

Loading…