Methanol → N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-2-fluoro-benzamide

HRID 10014

반응식

HRID 10014 반응식
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:20])[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].[F:21][C:22]1[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=1[C:24](Cl)=[O:25].CO>C1COCC1>[O:19]=[C:13]1[CH:12]([N:5]2[C:4](=[O:20])[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:24](=[O:25])[C:23]3[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=3[F:21])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

참가 물질

5

반응물 3

HCID 887MethanolHCID 98082-Fluorobenzoyl chlorideHCID 134780Pomalidomide

생성물 1

HCID 10111277N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-2-fluoro-benzamide수율 94.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (1.1 g, 4.0 mmol) and 2-fluorobenzoyl chloride (1.0 mL, 8.4 mmol) in THF (40 mL) 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 (20 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-2-fluoro-benzamide as a white solid (1.5 g, 93% yield): mp, 300–302° C.; 1H NMR (DMSO-d6) δ 2.05–2.12 (m, 1H, CHH), 2.45–2.65 (m, 2H, CH2), 2.83–2.97 (m, 1H, CHH), 5.18 (dd, J=5.5, 12.9 Hz, 1H, NCH), 7.40–7.49 (m, 2H, Ar), 7.67–7.76 (m, 2H, Ar), 7.88–7.98 (m, 1H, Ar), 8.01–8.05 (m, 1H, Ar), 8.76 (d, J=8.4 Hz, 1H Ar), 10.56 (d, JN-F=10 Hz, 1H, NH), 11.17 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.96, 30.92, 48.97, 116.48, 116.97 (d, JC-F=14 Hz), 118.82, 120.87 (d, JC-F=12 Hz), 125.32 (d, JC-F=1.5 Hz), 125.74, 131.32, 131.39, 134.88 (d, JC-F=9 Hz), 136.22, 136.48, 159.75 (d, JC-F=252 Hz), 161.76 (d, JC-F=7 Hz), 166.58, 168.04, 169.70, 172.71; Anal Calcd for C20H14N3O5F: C, 60.76; H, 3.57; N, 10.63; F, 4.81. Found: C, 60.70; H, 3.64; N, 10.64; F, 4.91.

후처리

  1. temperaturewas heated
  2. temperatureto reflux for 15 h
  3. customto give a suspension
  4. filtrationThe suspension was filtered
  5. washwashed with methanol (20 mL)

출처 및 근거

ORD 기록
ord-b70154211f7644a99ea0a75986065106
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091353B2

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