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

HRID 906735

반응식

HRID 906735 반응식
[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]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 8063PentanalHCID 216326LenalidomideHCID 5049666Sodium triacetoxyborohydride

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-df3a6e8fc03e4d6eaecc51494c764c98
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08012997B2

연결된 노트

불러오는 중…