1,1'-Carbonyldiimidazole → HCID 24964023, Verbindung

HRID 1409647Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1409647
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[CH3:8].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>[O:46]=[C:40]1[CH:39]([N:31]2[C:30](=[O:47])[C:29]3[C:34](=[CH:35][CH:36]=[CH:37][C:28]=3[CH2:27][NH:26][C:10](=[O:12])[CH2:9][C:4]3[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([F:1])[CH:3]=3)[N:33]=[C:32]2[CH3:38])[CH2:44][CH2:43][C:42](=[O:45])[NH:41]1

Komponenten

5

Edukt 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27746183-Fluoro-4-methylphenylacetic acidHCID 249683051015474-47-1

Produkt 1

HCID 24964023HCID 24964023, VerbindungAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of (3-fluoro-4-methyl-phenyl)-acetic acid (0.25 g, 1.5 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′carbonyldiimidazole (0.27 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 N-[3-(2,6-Dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-2-(3-fluoro-4-methyl-phenyl)-acetamide as a yellow solid (500 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, 6.10 min (99.3%); mp, 264-266° C.; 1HNMR (DMSO-d6)2.15-2.20 (m, 4H, CHH and CH3Ar), 2.57-2.91 (m, 6H, CHCH2, CH3), 3.51 (s, 2H, ArCH2), 4.73-4.78 (m, 2H, CH2NH), 5.23 (dd, J=6, 11 Hz, 1H, CH), 6.99-7.72 (m, 6H, Ar), 8.34 (t, J=6 Hz, 1H, CH2NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 13.76 (d, JC-F=3 Hz), 20.73, 23.27, 30.59, 41.60, 41.72, 56.48, 115.43 (d, JC-F=22 Hz), 117.69, 121.98 (d, JC-F=17 Hz), 124.82 (d, JC-F=7 Hz), 124.83, 125.59, 131.23 (d, JC-F=5 Hz), 133.80, 136.12 (d, JC-F=8 Hz), 140.64, 148.44, 154.80, 160.38 (d, JC-F=242 Hz), 160.91, 169.49, 169.90, 172.58. LCMS MH=451; Anal Calcd For C24H23N4O4F: C, 63.99; H, 5.15; N, 12.44; F, 4.22. Found: C, 63.61; H, 5.19; N, 12.33; F, 4.20.

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-84d29871f70c4ba489e2ea198625dba2
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921385B2

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