Dimethylformamide → N-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]-2-ethoxy-acetamide

HRID 906760

반응식

HRID 906760 반응식
[CH2:1]([O:3][CH2:4][C:5]([OH:7])=O)[CH3:2].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:19][C:20]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:21]=1[C:22](=[O:38])[N:23]([CH:30]1[CH2:35][CH2:34][C:33](=[O:36])[NH:32][C:31]1=[O:37])[C:24]2=[O:29]>CCOCC.CO.C1COCC1>[O:37]=[C:31]1[CH:30]([N:23]2[C:22](=[O:38])[C:21]3[C:25](=[CH:26][CH:27]=[CH:28][C:20]=3[NH:19][C:5](=[O:7])[CH2:4][O:3][CH2:1][CH3:2])[C:24]2=[O:29])[CH2:35][CH2:34][C:33](=[O:36])[NH:32]1

참가 물질

8

반응물 4

HCID 6228DimethylformamideHCID 12301Ethoxyacetic acidHCID 65578Oxalyl chlorideHCID 134780Pomalidomide

생성물 1

HCID 21988552N-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]-2-ethoxy-acetamide수율 90.4%

시약·촉매·용매 3

HCID 887Methanol용매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of ethoxyacetic acid (0.8 mL, 8.5 mmol) and oxalyl chloride (0.7 mL, 8.0 mmol) in ether (5 mL) was added DMF (0.03 mL) at room temperature. After 3 h, 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (1.1 g, 4.0 mmol) and THF (40 mL) was added to the mixture. Then the mixture was heated to reflux for 15 h. To the mixture was added methanol (10 mL) to give a suspension. The suspension was filtered and washed with methanol (10 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-2-ethoxy-acetamide as a white solid (1.3 g, 87% yield): mp, 253-255° C.; 1H NMR (DMSO-d6) δ 1.27 (t, J=7.0 Hz, 3H, CH3), 2.06-2.10 (m, 1H, CHH), 2.46-2.64 (m, 2H, CH2), 2.84-2.98 (m, 1H, CHH), 3.66 (q, J=7.0 Hz, 2H, CH2), 4.14 (s, 2H, CH2), 5.17 (dd, J=5.2, 12.7 Hz, 1H, NCH), 7.62 (d, J=7.2 Hz, 1H, Ar), 7.87 (t, J=8.2 Hz, 1H, Ar), 8.75 (d, J=8.4 Hz, 1H, Ar), 10.39 (s, 1H, NH), 11.16 (s, 1H, NH); 13C NMR (DMSO-d6) δ 14.88, 21.93, 30.92, 48.98, 66.89, 69.49, 116.00, 118.28, 124.25, 131.31, 135.99, 136.53, 166.69, 168.31, 169.49, 169.73, 174.71; Anal Calcd for C17H17N3O6: C, 56.82; H, 4.77; N, 11.69. Found: C, 56.82; H, 4.71; N, 11.60.

후처리

  1. temperatureThen the mixture was heated
  2. temperatureto reflux for 15 h
  3. customto give a suspension
  4. filtrationThe suspension was filtered
  5. washwashed with methanol (10 mL)

출처 및 근거

ORD 기록
ord-245476ad938d4739af4c43edadbe6d9d
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08012997B2

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