Methanol → N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)cyclopropanecarboxamide

HRID 10006

반응식

HRID 10006 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].[CH:21]1([C:24](Cl)=[O:25])[CH2:23][CH2:22]1.CO>C1COCC1.CCOCC>[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]([CH:21]3[CH2:23][CH2:22]3)=[O:25])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

참가 물질

6

반응물 3

HCID 887MethanolHCID 77637Cyclopropanecarbonyl chlorideHCID 134780Pomalidomide

생성물 1

HCID 10132095N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)cyclopropanecarboxamide수율 84%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (0.60 g, 2.2 mmol) and cyclopropanecarbonyl chloride (0.4 mL, 4.4 mmol) in THF (20 mL) was heated to reflux for 15 h. To the mixture was added methanol (5 mL). The solvent was removed in vacuo to give a solid. The solid was slurried in ether (30 mL0 for 1 h. The suspension was filtered and washed with ether (30 mL) to give cyclopropanecarboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-amide as a solid (630 mg, 84% yield): mp, 237–239° C.; 1H NMR (DMSO-d6) δ 0.87–0.90 (m, 4H, 2CH2), 1.93–2.09 (m, 2H, CH, CHH), 2.49–2.65 (m, 2H, CH2), 2.64–2.96 (m, 1H, CHH), 5.15 (dd, J=5.2, 12.6 Hz, 1H, NCH), 7.61 (d, J=7.2 Hz, 1H, Ar), 7.82 (t, J=7.7 Hz, 1H, Ar), 8.41 (d, J=8.3 Hz, 1H, Ar), 9.99 (s, 1H, NH), 11.16 (s, 1H, NH); 13C NMR (DMSO-d6) δ 8.10, 14.93, 22.00, 30.93, 48.92, 117.07, 118.30, 126.69, 131.49, 135.97, 136.43, 166.67, 167.57, 169.77, 172.55, 172.74; Anal Calcd for C17H15N3O5: C, 59.82; H, 4.43; N, 12.31. Found: C, 59.50; H, 4.39; N, 12.04.

후처리

  1. temperaturewas heated
  2. temperatureto reflux for 15 h
  3. customThe solvent was removed in vacuo
  4. customto give a solid
  5. customfor 1 h
  6. filtrationThe suspension was filtered
  7. washwashed with ether (30 mL)

출처 및 근거

ORD 기록
ord-3cc38ad9cd46421d88aff5f121abcc75
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091353B2

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