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

HRID 2376190ノート

反応式

HRID 2376190 の反応式
[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

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 86603704ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate

生成物 1

HCID 136335111(2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)-N-hydroxyacrylamide収率 8%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
0 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-fc3f16416e8b454caa7a58d8da1c9474
出典データセット
uspto-grants-2008_12
特許番号
US07465731B2

反応ノート

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