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1-Hydroxybenzotriazole → N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamide

HRID 1093657
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1093657
[C:1]1([NH:7][C:8]2[N:13]=[CH:12][C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=O)=[O:15])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[Cl:53][C:54]1[CH:66]=[CH:65][CH:64]=[CH:63][C:55]=1[O:56][CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>CN(C=O)C.O>[Cl:53][C:54]1[CH:66]=[CH:65][CH:64]=[CH:63][C:55]=1[O:56][CH:57]1[CH2:62][CH2:61][N:60]([C:18](=[O:20])[CH2:17][NH:16][C:14](=[O:15])[C:11]2[CH:10]=[CH:9][C:8]([NH:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:13][CH:12]=2)[CH2:59][CH2:58]1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167325894-(2-Chlorophenoxy)piperidine hydrochlorideHCID 57874437[(6-Phenylamino-pyridine-3-carbonyl)-amino]-acetic acid

Produkt 1

HCID 44233263
N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamide
Ausbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of [(6-phenylamino-pyridine-3-carbonyl)-amino]-acetic acid (0.035 g, 0.00013 mol) in DMF (1 mL) was added DIPEA (0.05 g, 0.00039 mol), HOBt (0.0209 g, 0.00015 mol) and EDCI.HCl (0.029 g, 0.0001549 mol) at ambient temperature. After 2 minutes 4-(2-chloro-phenoxy)-piperidine hydrochloride (0.0382 g, 0.00015 mol) and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (70% ethyl acetate in hexane) to afford 0.037 g (62%) of N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamide. LCMS: 465.16 (M+1)+, 96.6%, 1H NMR (DMSO-d6): δ 9.4 (s, 1H), 8.8 (s, 1H), 8.4 (t, 1H), 8.0 (dd, 1H), 7.7 (d, 2H), 7.45 (d, 1H), 7.4 (m, 4H), 7.0 (d, 2H), 6.8 (d, 1H), 4.7 (m, 1H), 4.25 (m, 2H), 3.7 (m, 2H), 3.5 (m, 2H), 2.0 (m, 2H), 1.7 (q, 2H).

Aufarbeitung

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-9245217ea5514f97a0b8a18446a366cd
Quelldatensatz
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08129376B2

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