Benzaldehyde → 3-{1-Oxo-4-[benzylamino]isoindolin-2-yl}piperidine-2,6-dione

HRID 9962

反応式

HRID 9962 の反応式
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[CH:20](=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[BH4-].[Na+]>CO.C(O)(=O)C>[O:11]=[C:6]1[C:7]2[C:3](=[C:2]([NH:1][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:10]=[CH:9][CH:8]=2)[CH2:4][N:5]1[CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19]

参加物

6

反応物 3

HCID 240BenzaldehydeHCID 216326LenalidomideHCID 4311764Sodium borohydride

生成物 1

HCID 102914653-{1-Oxo-4-[benzylamino]isoindolin-2-yl}piperidine-2,6-dione収率 60.1%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 887Methanol溶媒

実験手順

A stirred mixture of 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (518 mg, 2.0 mmol) and benzaldehyde (0.21 ml, 2.0 mmol) in methanol (20 ml) was heated to reflux for 5 h. The solvent was removed in vacuo to give a solid. The solid was re-dissolved in acetic acid (20 ml). The stirred solution was heated to reflux for 1 h, and was then allowed to cool to room temperature. To the stirred solution was added sodium borohydride (90 mg, 2.3 mmol) and stirring continued at room temperature for 18 h. The resulting suspension was filtered and washed with acetic acid (10 ml) and ether (20 ml) to give 3-{1-oxo-4-[benzylamino]isoindolin-2-yl}piperidine-2,6-dione as an off-white solid (420 mg, 60% yield): mp, 257–259° C.; 1H NMR (DMSO-d6) δ 2.01–2.07 (m, 1H, CHH), 2.23–2.30 (m, 1H, CHH), 2.49–2.65 (m, 1H, CHH), 2.85–3.00 (m, 1H, CHH), 4.19 (d, J=17 Hz, 1H, CHH), 4.31 (d, J=17 Hz, 1H, CHH), 4.39 (d, J=5.7 Hz, 2H, CH2), 5.12 (dd, J=5.1, 13 Hz, 1H, NCH), 6.37 (t, J=5.9 Hz, 1H, NH), 6.62 (d, J=8.0 Hz, 1H, Ar), 6.91 (d, J=7.3 Hz, 1H, Ar), 7.19–7.40 (m, 6H, Ar), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.79, 31.25, 45.79, 46.09, 51.56, 110.32, 112.34, 126.72, 127.05, 128.32, 129.07, 132.08, 139.72, 143.33, 168.82, 171.22, 172.90; Anal Calcd for C20H19N3O3: C, 68.75; H, 5.48; N, 12.03. Found C, 68.73; H, 5.41; N, 12.04.

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 5 h
  3. customThe solvent was removed in vacuo
  4. customto give a solid
  5. temperatureThe stirred solution was heated
  6. temperatureto reflux for 1 h
  7. filtrationThe resulting suspension was filtered
  8. washwashed with acetic acid (10 ml) and ether (20 ml)

出典と根拠

ORDレコード
ord-cd0e622d7e2b4c538ea2130286c65fec
出典データセット
uspto-grants-2006_08
特許番号
US07091353B2

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