3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxo-piperidin-3-yl)-4-(3-methoxy-phenylamino)-isoindole-1,3-dione

HRID 448411ノート

反応式

HRID 448411 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10]2[CH:18]=[CH:17][CH:16]=[C:12]([C:13]([OH:15])=O)[C:11]=2[C:19]([OH:21])=O)[CH:6]=[CH:7][CH:8]=1.Cl.[NH2:23][CH:24]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:25]1=[O:26]>N1C=CC=CC=1>[O:26]=[C:25]1[CH:24]([N:23]2[C:19](=[O:21])[C:11]3[C:12](=[CH:16][CH:17]=[CH:18][C:10]=3[NH:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:13]2=[O:15])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

参加物

4

反応物 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 58307244HCID 58307244、化合物

生成物 1

HCID 588272712-(2,6-Dioxo-piperidin-3-yl)-4-(3-methoxy-phenylamino)-isoindole-1,3-dione収率 76.7%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

実験手順

A mixture of 3-(3-methoxy-phenylamino)-phthalic acid (0.32 g, 1.1 mmol) and rac-α-aminoglutarimide hydrochloride (0.18 g, 1.1 mmol) in pyridine (10 mL) was heated to reflux for 15 hours. The reaction mixture was cooled, and the solvent was evaporated in vacuo. The residue was suspended in ethyl acetate (100 mL) and washed with dilute aqueous HCl (2×100 mL) and water (2×100 mL). Solvent was evaporated in vacuo. The residue was purified by ISCO silica gel flash chromatography using a methanol-methylene chloride gradient, eluting the product at 5:95 methanol-methylene chloride to give the title product (0.32 g, 76% yield): mp 210-212° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 60/40 CH3CN/0.1% H3PO4, 2.70 (97.39%); 1H NMR (DMSO-d6) δ 2.04-2.08 (m, 1H), 2.49-2.64 (m, 2H), 2.84-2.94 (m, 1H), 3.75 (s, 3H), 5.13 (dd, J=12.6 Hz, J=5.4 Hz, 1H), 6.71 (dd, J=8.4 Hz, J=2.2 Hz, 1H), 6.90-6.92 (m, 2H), 7.25-7.32 (m, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.60-7.66 (m, 1H), 8.42 (s, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 22.1, 31.0, 48.7, 55.1, 107.3, 109.6, 112.2, 113.6, 119.9, 130.2, 132.5, 136.2, 140.7, 142.6, 160.2, 167.0, 168.2, 170.0, 172.8; Anal. calcd for C20H17N3O5: C, 63.32; H, 4.52; N, 11.08. Found: C, 63.22; H, 4.51; N, 10.78.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 15 hours
  3. temperatureThe reaction mixture was cooled
  4. customthe solvent was evaporated in vacuo
  5. washwashed with dilute aqueous HCl (2×100 mL) and water (2×100 mL)
  6. customSolvent was evaporated in vacuo
  7. customThe residue was purified by ISCO silica gel flash chromatography
  8. washeluting the product at 5:95 methanol-methylene chloride

出典と根拠

ORDレコード
ord-4f108d453da6468c873951de43837489
出典データセット
uspto-grants-2013_07
特許番号
US08481568B2

反応ノート

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