Acetonitrile → N-[[2-[(3S)-3-Methyl-2,6-dioxopiperidin-3-YL]-1,3-dioxoisoindolin-5-YL]methyl]-4-(methylsulfonyl) benzamide

HRID 331548

Reaktionsgleichung

Reaktionsgleichung von HRID 331548
[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:27][CH2:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[C:34](=[O:38])[N:33]([C@@:39]1([CH3:47])[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]1=[O:46])[C:32]2=[O:48].CC#N>CN(C=O)C>[CH3:47][C@:39]1([N:33]2[C:32](=[O:48])[C:31]3[C:35](=[CH:36][CH:37]=[C:29]([CH2:28][NH:27][C:9](=[O:11])[C:8]4[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:13][CH:12]=4)[CH:30]=3)[C:34]2=[O:38])[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]1=[O:46]

Komponenten

6

Edukt 4

HCID 6342AcetonitrileHCID 682631,1'-CarbonyldiimidazoleHCID 77670p-(Methylsulphonyl)benzoic acidHCID 670196915-aminomethyl-2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-isoindole-1,3-dione hydrochloride

Produkt 1

HCID 24788309N-[[2-[(3S)-3-Methyl-2,6-dioxopiperidin-3-YL]-1,3-dioxoisoindolin-5-YL]methyl]-4-(methylsulfonyl) benzamideAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

A mixture of 4-(methylsulfonyl)benzoic acid (0.40 g, 2.0 mmol) and CDI (0.36 g, 2.2 mmol) in DMF (20 mL) was stirred under nitrogen at 40° C. for 2 hours. Then, 5-aminomethyl-2-[(3S)-3-methyl-2,6-dioxo-piperidin-3-yl]-isoindole-1,3-dione hydrochloride (0.67 g, 2.0 mmol) was added, and stirring proceeded at this temperature for an additional 2 hours. The mixture was cooled to room temperature, and was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The organic phase was washed with saturated aqueous sodium bicarbonate solution (2×100 mL) and evaporated. The residue was chromatographed on silica gel using 99:1 methylene chloride-methanol as the mobile phase, providing 0.30 g, in 32% yield. The product was obtained as a white solid; mp 165.5-167.5° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 4.08 (96.23%); 1H NMR (DMSO-d6) δ 2.09 (s, 3H), 2.22-2.28 (m, 1H), 2.73-2.95 (m, 3H), 3.47 (s, 3H), 4.86 (d, J=5.7 Hz, 2H), 7.98-8.04 (m, 3H), 8.25 (d, J=8.7 Hz, 2H), 8.32 (d, J=8.7 Hz, 2H), 9.58 (t, J=5.7 Hz, 1H), 11.21 (s, 1H); 13C NMR (DMSO-d6) δ 23.0, 30.6, 31.1, 44.8, 45.6, 60.8, 123.7, 125.2, 129.2, 130.3, 131.7, 133.4, 135.5, 140.4, 145.2, 149.0, 167.2, 169.7, 169.9, 174.1, 174.2; Anal. Calcd for C23H21N3O7S+0.3H2O: C, 56.50; H, 4.45; N, 8.59. Found: C, 56.61; H, 4.42; N, 8.30.

Aufarbeitung

  1. stirringstirring
  2. waitproceeded at this temperature for an additional 2 hours
  3. temperatureThe mixture was cooled to room temperature
  4. customwas partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL)
  5. washThe organic phase was washed with saturated aqueous sodium bicarbonate solution (2×100 mL)
  6. customevaporated
  7. customThe residue was chromatographed on silica gel using 99:1 methylene chloride-methanol as the mobile phase
  8. customproviding 0.30 g
  9. customThe product was obtained as a white solid

Quellen und Nachweise

ORD-Eintrag
ord-ae998d01eeae4308b925c24abaa46efe
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877780B2

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