Acetic Acid → 3-[1-Oxo-4-(pentylamino)isoindolin-2-yl]piperidine-2,6-dione

HRID 9991

反応式

HRID 9991 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)[CH2:21][CH2:22][CH2:23][CH3:24].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN(C=O)C.C(OCC)(=O)C>[O:11]=[C:6]1[C:7]2[C:3](=[C:2]([NH:1][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[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

7

反応物 4

HCID 176Acetic AcidHCID 8063PentanalHCID 216326LenalidomideHCID 5049666Sodium triacetoxyborohydride

生成物 1

HCID 98586673-[1-Oxo-4-(pentylamino)isoindolin-2-yl]piperidine-2,6-dione収率 21.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.52 g, 2.0 mmol) in DMF (10 ml) was added pentanal (0.26 g, 3.0 mmol), acetic acid (0.24 g, 4.0 mmol), and sodium triactoxyborohydride (0.85 g, 4.0 mmol). The reaction mixture was stirred at room temperature for 6 hours. The solvent was evaporated in vacuo and the residue was dissolved in ethyl acetate (100 ml), washed with H2O (3×100 ml), brine (1×100 ml), and dried over MgSO4. The solvent was evaporated and the residue was partially purified by chromatography (ethyl acetate/hexane, 75:25) to give an off-white solid which was slurried in ethyl acetate and filtered to give 0.14 g (21%) of product as a white solid: mp 244–246° C.; 1H NMR (DMSO-d6) δ 11.00 (s, 1H), 7.28 (t, J=7.7 Hz, 1H), 6.92 (d, J=7.3 Hz, 1H), 6.73 (d, J=8.0 Hz, 1H), 5.54 (t, J=5.3 Hz, 1H), 5.12 (dd, J=5.1 and 13.2 Hz, 1H), 4.24 (d, J=17.2 Hz, 1H), 4.13 (d, J=17.2 Hz, 1H) 3.15–3.07 (m, 2H), 3.00–2.86 (m, 1H), 2.65–2.59 (m, 1H), 2.39–2.23 (m, 1H), 2.08–1.99 (m, 1H), 1.61–1.57 (m, 2H), 1.41–1.32 (m, 4H), 0.89 (t, J=6.8 Hz, 3H); 13C NMR (DMSO-d6) δ 172.83, 171.19, 168.86, 143.74, 132.00, 129.15, 126.42, 111.66, 109.86, 51.46, 45.69, 42.68, 31.20, 28.80, 28.21, 22.79, 21.96, 13.89; Anal. Calcd. For C18H23N3O3: C, 65.63; H, 7.04; N, 12.76. Found: C, 65.69; H, 7.22; N, 12.55.

後処理

  1. customThe solvent was evaporated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
  3. washwashed with H2O (3×100 ml), brine (1×100 ml)
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated
  6. customthe residue was partially purified by chromatography (ethyl acetate/hexane, 75:25)
  7. customto give an off-white solid which
  8. filtrationfiltered

出典と根拠

ORDレコード
ord-85144f34d979457fac13774a460cb8d8
出典データセット
uspto-grants-2006_08
特許番号
US07091353B2

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