Hydrochloric Acid → (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)-N-hydroxyacrylamide

HRID 2376190Notes

Reaction equation

[CH2:1]([O:8][N:9]1[C:14](=[O:15])[CH2:13][CH2:12][C@@H:11]([NH:16][C:17]2[N:18]=[CH:19][C:20](/[CH:23]=[CH:24]/[C:25](OCC)=[O:26])=[N:21][CH:22]=2)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:31][OH:32].C[O-].[Na+].Cl>CO>[CH2:1]([O:8][N:9]1[C:14](=[O:15])[CH2:13][CH2:12][C@@H:11]([NH:16][C:17]2[N:18]=[CH:19][C:20](/[CH:23]=[CH:24]/[C:25]([NH:31][OH:32])=[O:26])=[N:21][CH:22]=2)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate (200 mg, 0.50 mmol) in methanol (5 mL) was added hydroxylamine hydrochloride (175 mg, 2.52 mmol) at ambient temperature under nitrogen. After cooling, 1M sodium methanolate in methanol (5 mL) was added dropwise to the mixture over 1 h, the reaction mixture was stirred at 0° C. for 2 hrs and at ambient temperature for 4 hrs. The reaction mixture was adjusted to PH 6.0 with 1 mol/L hydrochloric acid and evaporated in vacuo. The residue was dissolved in ethanol and the precipitate was removed by filtration. The solvent was evaporated in vacuo. The residue was purified by preparative HPLC (CH3CN, 20% NH4HCO3/30%-90%, gradient) to give (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)-N-hydroxyacrylamide (15 mg, 8%) as a powder.

Workup

temperatureAfter cooling
customevaporated in vacuo
dissolutionThe residue was dissolved in ethanol
customthe precipitate was removed by filtration
customThe solvent was evaporated in vacuo
customThe residue was purified by preparative HPLC (CH3CN, 20% NH4HCO3/30%-90%, gradient)

Sources & evidence

ORD record: ord-fc3f16416e8b454caa7a58d8da1c9474
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07465731B2

Reaction notes

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