Hydroxyamine hydrochloride → HCID 86645982, compound

HRID 1094329Notes

Reaction equation

HRID 1094329 reaction equation
[OH:1][NH:2][CH:3]([C@@H:6]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[S:16][CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=2)=[CH:10][CH:9]=1)[CH3:7])[C:4]#[N:5].Cl.[NH2:25]O.C([O-])(=O)C.[Na+]>CCO>[F:22][C:20]([F:23])([F:21])[C:18]1[N:19]=[C:15]([NH:14][C:11]2[CH:10]=[CH:9][C:8]([C@H:6]([C:3]3[C:4]([NH2:25])=[N:5][O:1][N:2]=3)[CH3:7])=[CH:13][CH:12]=2)[S:16][CH:17]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 86645983HCID 86645983, compound

Product 1

HCID 86645982HCID 86645982, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of intermediate 13a (0.738 gr, 2.16 mmol), hydroxylamine hydrochloride (83 mg, 2.50 mmol) and sodium acetate (410 mg, 5 mmol) in EtOH (15 ml) was refluxed for 4 h. After cooling, the precipitate was collected by filtration and dried. The precipitated α-oximido-acetamidoxime sodium acetate derivative was refluxed with excess PCl5 in dry Et2O (15 ml) for 6 h. After cooling at room temperature the reaction was quenched with a buffered solution at pH 8.2 (10 ml) and the two phases separated. The aqueous layer was extracted with Et2O (2×10 ml) and the collected organic phases were dried over anhydrous Na2SO4 and evaporated under vacuum to give 4-[(1R)-1-{4-[(4-(trifluoromethyl)-1,3-thiazol-2-yl)amino]phenyl}ethyl]-1,2,5-oxadiazol-3-amine (0.57 g, 1.62 mmol) as a white solid (75%). 1H-NMR (DMSO-d6): δ 8.25 (bs, 1H, NH), 7.40 (d, 2H, J=7 Hz), 7.25 (d, 2H, J=7 Hz), 7.05 (s, 1H), 5.15 (bs, 2H, NH2), 3.90 (q, 1H, J=7 Hz), 1.75 (d, 3H, J=7 Hz).

Workup

  1. temperaturewas refluxed for 4 h
  2. temperatureAfter cooling
  3. filtrationthe precipitate was collected by filtration
  4. customdried
  5. temperatureThe precipitated α-oximido-acetamidoxime sodium acetate derivative was refluxed with excess PCl5 in dry Et2O (15 ml) for 6 h
  6. customwas quenched with a buffered solution at pH 8.2 (10 ml)
  7. customthe two phases separated
  8. extractionThe aqueous layer was extracted with Et2O (2×10 ml)
  9. dry with materialthe collected organic phases were dried over anhydrous Na2SO4
  10. customevaporated under vacuum

Sources & evidence

ORD record
ord-5d0289ec49934b3590dda5bebcfa8da4
Source dataset
uspto-grants-2012_03
Patent number
US08133911B2

Reaction notes

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