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

HRID 448488Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 448488
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.[OH:34]N1C2C=CC=CC=2N=N1.[CH3:44][C:45]1[CH:46]=C(C(O)=O)[O:48][C:49]=1[CH3:50].Cl.CN(C)[CH2:57][CH2:58][CH2:59]N=C=NCC>C(#N)C>[CH3:46][C:45]1[CH:44]=[C:59]([CH2:58][C:57]([NH:2][CH2:3][C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:5]=2[C:6](=[O:22])[N:7]([CH:14]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]2=[O:21])[C:8]3=[O:13])=[O:34])[O:48][C:49]=1[CH3:50]

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27749244,5-Dimethylfuran-2-carboxylic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Produkt 1

HCID 672288652-(4,5-dimethyl-furan-2-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamideAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

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 4,5-dimethyl-2-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), 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-(4,5-dimethyl-furan-2-yl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (0.6 g, 72%) as a white solid: mp 221-223° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=2.85 min. (99%); 1H NMR (DMSO-d6) δ 1.95 (s, 3H), 2.05-2.11 (m, 1H), 2.26 (s, 3H), 2.52-2.64 (m, 2H), 2.85-2.97 (m, 1H), 4.86 (d, J=6.0 Hz, 2H), 5.13-5.19 (dd, J=5.3 and 12.6 Hz, 1H), 6.95 (s, 1H), 7.65-7.85 (m, 3H), 8.81 (t, J=6.0 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 9.41, 11.41, 21.96, 30.91, 37.55, 48.84, 116.30, 117.01, 121.80, 127.01, 131.48, 132.88, 134.76, 139.33, 144.63, 150.08, 158.18, 166.95, 167.52, 169.81, 172.74; Anal. Calcd. for C21H19N3O6: C, 61.61; H, 4.68; N, 10.36. Found: C, 61.63; H, 4.43; N, 10.03.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-52e8ecda9a4d4de1a8e6621f2f0812d9
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481568B2

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