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

HRID 10000

반응식

HRID 10000 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:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[C:25](Cl)=[O:26].CO>C1COCC1.C(OCC)C>[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:25](=[O:26])[C:24]3[CH:28]=[CH:29][CH:30]=[C:22]([F:21])[CH:23]=3)[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

참가 물질

6

반응물 3

HCID 887MethanolHCID 743763-Fluorobenzoyl chlorideHCID 134780Pomalidomide

생성물 1

HCID 10294074N-[2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-3-fluoro-benzamide수율 96%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

To a suspension of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (0.55 g, 2 mmol) in THF (30 ml) was added 3-Fluorobenzoyl chloride (0.49 ml, 4 mmol). The mixture was heated to reflux for 18 hours. The reaction was cooled to room temperature, methanol (2 ml) was added, and the mixture stirred for 1 hour. The solvent was evaporated in vacuo leaving a solid which was slurried in diethyl ether (20 ml) and filtered to give 0.69 g (96%) of product as an off-white solid: mp 260–262° C.; 1H NMR (DMSO-d6) d 11.00 (s, 1H), 10.39 (s, 1H), 8.53 (d, J=8.3 Hz, 1H), 7.94–7.50 (m, 6H), 5.15 (dd, J=5.6 and 12.7 Hz, 1H), 2.97–2.83 (m, 1H), 2.66–2.49 (m, 2H), 2.14–2.06 (m, 1H); 13C NMR (DMSO-d6) d 172.36, 169.36, 167.66, 166.39, 163.62, 136.03, 131.31, 131.12, 130.99, 126.60, 123.19, 123.15, 119.44, 119.11, 118.89, 118.42, 114.31, 113.94, 48.91, 30.77, 21.83; Anal. Calcd. For C20H14FN3O5: C, 60.76; H, 3.57; N, 10.63. Found: C, 60.88; H, 3.38; N, 10.51.

후처리

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 hours
  3. customThe solvent was evaporated in vacuo
  4. customleaving a solid which
  5. filtrationfiltered

출처 및 근거

ORD 기록
ord-fa22e2a72a7b41c18b5774c454221a27
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091353B2

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