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

HRID 906755

反応式

HRID 906755 の反応式
[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

参加物

6

反応物 3

HCID 887MethanolHCID 77637Cyclopropanecarbonyl chlorideHCID 134780Pomalidomide

生成物 1

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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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 mL) 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.

後処理

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

出典と根拠

ORDレコード
ord-8f2da509c7924fb4a5bf040c8ebcc6c6
出典データセット
uspto-grants-2011_09
特許番号
US08012997B2

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