2,5-Dimethyl-3-furoic acid → 2-(2,5-dimethyl-furan-3-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide

HRID 448489

反応式

HRID 448489 の反応式
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].N12CCCN=C1CCCCC2.ON1C2C=CC=CC=2N=N1.CC1[O:46][C:47]([CH3:53])=[CH:48][C:49]=1[C:50](O)=[O:51].Cl.CN(C)[CH2:57][CH2:58][CH2:59]N=C=NCC>C(#N)C>[CH3:53][C:47]1[O:46][C:58]([CH3:57])=[CH:59][C:48]=1[CH2:49][C:50]([NH:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13])=[O:51]

参加物

7

反応物 5

HCID 694652,5-Dimethyl-3-furoic acidHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

生成物 1

HCID 672289192-(2,5-dimethyl-furan-3-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide収率 73%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in acetonitrile (60 mL), was added 1,8-diazabicyclo[5,4,0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzotriazole (0.4 g, 2.6 mmol) and 2,5-dimethyl-3-furoic acid (0.3 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 g, 3.2 mmol). The mixture was stirred at room temperature overnight and was concentrated in vacuo. The residue was dissolved in CH2Cl2 (80 mL) and washed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL), and dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2 3:7) to afford 2-(2,5-dimethyl-furan-3-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (0.65 g, 73%) as a white solid: mp 193-195° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.45 min. (99%); 1H NMR (DMSO-d6) δ 2.06-2.11 (m, 1H), 2.23 (s, 3H), 2.46 (s, 3H), 2.54-2.63 (m, 2H), 2.85-2.97 (m, 1H), 4.85 (d, J=5.9 Hz, 2H), 5.14-5.20 (dd, J=5.3 and 12.6 Hz, 1H), 6.49 (s, 1H), 7.67-7.86 (m, 3H), 8.54 (t, J=5.9 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 12.98, 13.08, 21.96, 30.92, 37.53, 48.85, 104.86, 115.84, 121.77, 126.99, 131.48, 132.99, 134.76, 139.69, 149.11, 154.47, 163.32, 166.96, 167.54, 169.81, 172.74; Anal. Calcd. for C21H19N3O6: C, 61.61; H, 4.68; N, 10.26. Found: C, 61.66; H, 4.37; N, 9.99.

後処理

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationwas concentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
  4. washwashed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL)
  5. dry with materialdried over MgSO4
  6. customSolvent was removed in vacuo
  7. customthe residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2 3:7)

出典と根拠

ORDレコード
ord-9c6eb2a8fb8f4166aa08a21742d2e165
出典データセット
uspto-grants-2013_07
特許番号
US08481568B2

関連ノート

読み込み中…