Aniline → 5-Cyano-N-[4-(4-Methylpiperazin-1-Yl)-2-Piperidin-1-Ylphenyl]furan-2-Carboxamide

HRID 646845

Reaktionsgleichung

Reaktionsgleichung von HRID 646845
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[C:10]([N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH:9]=2)[CH2:4][CH2:3]1.NC1C=CC=CC=1.[C:30]([C:32]1[O:36][C:35]([C:37](O)=[O:38])=[CH:34][CH:33]=1)#[N:31].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>[Pd].CN(C=O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:37]([C:35]3[O:36][C:32]([C:30]#[N:31])=[CH:33][CH:34]=3)=[O:38])=[C:10]([N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH:9]=2)[CH2:4][CH2:3]1

Komponenten

8

Edukt 5

HCID 6115AnilineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 28857041-Methyl-4-(4-nitro-3-(piperidin-1-yl)phenyl)piperazineHCID 108555165-cyanofuran-2-carboxylic Acid

Produkt 1

HCID 115028715-Cyano-N-[4-(4-Methylpiperazin-1-Yl)-2-Piperidin-1-Ylphenyl]furan-2-Carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

The procedure of Example 4, step (c) was followed using 304 mg (1.00 mmol) 1-methyl-4-(4-nitro-3-piperidin-1-yl-phenyl)-piperazine (as prepared in the previous step) and 304 mg of 10% palladium on carbon (50% by weight water) to prepare the intermediate aniline (4-(4-methyl-piperazin-1-yl)-2-piperidin-1-yl-phenylamine) along with 140 mg (1.02 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 178 μL (2.04 mmol) of oxalyl chloride, 10 μL of anh DMF, and 267 μL (1.53 mmol) of DIEA to perform the amide coupling. The resulting residue was chromatographed on a 20-g silica SPE column with 2-5% EtOH-dichloromethane to afford, after slow concentration from EtOAc-hexane (1:1), 232 mg (59%) of the title compound as a yellow solid: 1H-NMR (CDCl3; 400 MHz): δ 9.53 (br s, 1H), 8.32 (d, 1H, J=8.9 Hz), 7.25 (d, 1H, J=3.7 Hz, partially obscured by CHCl3 peak), 7.21 (d, 1H, J=3.7 Hz), 6.80 (d, 1H, J=2.7 Hz), 6.73 (dd, 1H, J=8.9, 2.7 Hz), 3.20 (m, 4H), 2.85 (m, 4H), 2.59 (m, 4H), 2.36 (s, 3H), 1.80 (m, 4H), and 1.65 (br m, 2H). Mass spectrum (ESI, m/z): Calcd. for C22H27N5O2, 394.2 (M+H), found 394.2.

Aufarbeitung

  1. customThe resulting residue was chromatographed on a 20-g silica SPE column with 2-5% EtOH-dichloromethane
  2. customto afford
  3. concentrationafter slow concentration from EtOAc-hexane (1:1), 232 mg (59%) of the title compound as a yellow solid

Quellen und Nachweise

ORD-Eintrag
ord-2d5c5329a6f44672b97f183fc9f9fdb0
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07705042B2

Verknüpfte Notizen

Wird geladen…