1,1'-Carbonyldiimidazole → HCID 24963329, Verbindung

HRID 1409645Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1409645
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:26][CH2:27][C:28]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:29]=1[C:30](=[O:47])[N:31]([CH:39]1[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]1=[O:46])[C:32]([CH3:38])=[N:33]2>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:26][CH2:27][C:28]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:29]=2[C:30](=[O:47])[N:31]([CH:39]2[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]2=[O:46])[C:32]([CH3:38])=[N:33]3)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

Komponenten

5

Edukt 3

HCID 682631,1'-CarbonyldiimidazoleHCID 798743,4-Dichlorophenylacetic acidHCID 249683051015474-47-1

Produkt 1

HCID 24963329HCID 24963329, VerbindungAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of (3,4-dichloro-phenyl)-acetic acid (0.30 g, 1.5 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′carbonyldiimidazole (0.26 g, 1.6 mmol) and stirred for one hour. To the mixture, 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.50 g, 1.5 mmol) was added, and the mixture was stirred for 15 minutes. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give 2-(3,4-dichloro-phenyl)-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-acetamide as a yellow solid (540 mg, 74% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, grad. to 95/5 in 5 min, kept 5 min, 6.41 min (98.4%); mp, 262-264° C.; 1HNMR (DMSO-d6)2.14-2.19 (m, 1H, CHH), 2.57-2.89 (m, 6H, CHCH2, CH3), 3.57 (s, 2H, ArCH2), 4.69-4.85 (m, 2H, CH2NH), 5.24 (dd, J=6, 11 Hz, 1H, CH), 7.26-7.73 (m, 6H, Ar), 8.42 (t, J=6 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.73, 23.28, 30.60, 40.98, 41.76, 56.49, 117.70, 124.84, 125.65, 129.06, 129.55, 130.27, 130.63, 131.11, 133.82, 137.43, 140.52, 148.46, 154.81, 160.90, 169.42, 169.49, 172.59. LCMS MH=487, 489; Anal Calcd For C23H20N4O4Cl2: C, 56.69; H, 4.14; N, 11.50; Cl, 14.55. Found: C, 56.50; H, 3.95; N, 11.25; Cl, 14.29.

Aufarbeitung

  1. stirringthe mixture was stirred for 15 minutes
  2. customThe solvent was evaporated
  3. customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Quellen und Nachweise

ORD-Eintrag
ord-75b0f98f46334ee197362932283c33d1
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921385B2

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