3-Chlorobenzaldehyde → 3-[4-(3-Chloro-benzylamino)-1-oxo-1,3-dihydro-isoindol-2-yl]-piperidine-2,6-dione

HRID 10053

Reaktionsgleichung

Reaktionsgleichung von HRID 10053
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][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].[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH:24]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)Cl.CO>C(O)(=O)C.C(Cl)Cl>[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH2:24][NH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][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]

Komponenten

7

Edukt 4

HCID 114773-ChlorobenzaldehydeHCID 216326LenalidomideHCID 5049666Sodium triacetoxyborohydrideHCID 21226129Dichloromethane methanol

Produkt 1

HCID 219885613-[4-(3-Chloro-benzylamino)-1-oxo-1,3-dihydro-isoindol-2-yl]-piperidine-2,6-dioneAusbeute 31,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

3-(4-Amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (1.04 g, 4 mmol) was dissolved in acetic acid (7 ml) with heat. The mixture was cooled slightly and methylene chloride (50 ml) was added slowly followed by 3-chlorobenzaldehyde (0.91 ml, 8 mmol) and sodium triacetoxyborohydride (2.54 g, 12 mmol). The reaction mixture was stirred at room temperature under a nitrogen atomosphere for 2 h, diluted with methylene chloride (100 ml), washed with water (2×100 ml), saturated aqueous sodium bicarbonate (2×100 ml), brine (100 ml), dried (magnesium sulfate), and filtered. The solvent was evaporated in vacuo to give a white solid. The solid was recystallized from methylene chloride/methanol to give 0.48 g (31%) of product as a white solid. mp 253–255° C.; 1H NMR (DMSO-d6) δ 11.05 (s, 1H), 7.45 (s, 1H), 7.37–7.19 (m, 4H), 6.95 (d, J=7.4 Hz, 1H), 6.63 (d, J=8.0 Hz, 1H), 6.45 (t, J=5.9 Hz, 1H), 5.14 (dd, J=5.1 and 13.1 Hz, 1H), 4.41 (d, J=5.8 Hz, 2H), 4.34 (d, J=17.3 Hz, 1H), 4.20 (d, J=17.2 Hz, 1H) 3.01–2.87 (m, 1H), 2.66–2.60 (m, 1H), 2.42–2.25 (m, 1H), 2.08–2.04 (m, 1H); 13C NMR (DMSO-d6) δ 172.90, 171.24, 168.74, 143.03, 142.59, 133.08, 132.16, 130.19, 129.12, 126.80, 126.70, 125.73, 112.27, 110.55, 51.54, 45.73, 45.47, 31.25, 22.79; Anal. Calcd. For C20H18ClN3O3: C, 62.58; H, 4.73; N, 10.95. Found: C, 62.32; H, 4.61; N, 10.80.

Aufarbeitung

  1. temperaturewith heat
  2. temperatureThe mixture was cooled slightly
  3. washwashed with water (2×100 ml), saturated aqueous sodium bicarbonate (2×100 ml), brine (100 ml)
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customThe solvent was evaporated in vacuo
  7. customto give a white solid

Quellen und Nachweise

ORD-Eintrag
ord-1cc65329f18949559358be5e5faca254
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091353B2

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