StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Water → 6-Ethoxy-pyridazine-3-carboxylic acid n-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-6-ethoxy-nicotinamide

HRID 331577
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 331577
[CH2:1]([O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=1)[CH3:2].C1N=C[N:15](C(N2C=NC=C2)=O)C=1.CS(O)(=O)=O.[NH2:30][CH2:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[C:37](=[O:41])[N:36]([CH:42]1[CH2:47][CH2:46][C:45](=[O:48])[NH:44][C:43]1=[O:49])[CH2:35]2.O>CN(C)C=O>[O:49]=[C:43]1[CH:42]([N:36]2[CH2:35][C:34]3[C:38](=[CH:39][CH:40]=[C:32]([CH2:31][NH:30][C:8](=[O:10])[C:7]4[CH:11]=[CH:12][C:4]([O:3][CH2:1][CH3:2])=[N:5][CH:6]=4)[CH:33]=3)[C:37]2=[O:41])[CH2:47][CH2:46][C:45](=[O:48])[NH:44]1.[CH2:1]([O:3][C:4]1[N:5]=[N:15][C:7]([C:8]([OH:10])=[O:9])=[CH:11][CH:12]=1)[CH3:2]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 64858176-Ethoxypyridine-3-carboxylic acidHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Produkt 1

HCID 670231656-Ethoxy-pyridazine-3-carboxylic acid n-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-6-ethoxy-nicotinamide
Ausbeute 72,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

A stirred mixture of 6-ethoxy-nicotinic acid (0.23 g, 1.40 mmol) and CDI (0.24 g, 1.50 mmol) in N,N-dimethylformamide (10 mL) was heated to 40° C. under nitrogen. After 1 h, 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate (0.5 g, 1.40 mmol) was added and the mixture was heated at 50° C. for 1.5 h. The mixture was cooled to rt and water (20 mL) was added. The solids were isolated by filtration and then triturated in EtOAc (20 mL) for 18 h. The product was filtered and dried in vacuo to give 6-ethoxy-pyridazine-3-carboxylic acid N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-6-ethoxy-nicotinamide as a white solid (0.30 g, 53% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 to 90/10 CH3CN/0.1% H3PO4 gradient over 15 mins, 7.12 min (95.33%); mp: 255-257° C.; 1H NMR (DMSO-d6) δ 1.33 (t, J=7.1 Hz, 3H, CH3), 1.84-2.14 (m, 1H, CHH), 2.27-2.47 (m, 1H, CHH), 2.60 (d, J=16.8 Hz, 1H, CHH), 2.80-3.09 (m, 1H, CHH), 4.21-4.52 (m, 4H, CH2, CH2), 4.59 (d, J=5.9 Hz, 2H, CH2), 5.11 (dd, J=5.1, 13.2 Hz, 1H, CH), 6.88 (d, J=8.7 Hz, 1H, Ar), 7.47 (d, J=7.9 Hz, 1H, Ar), 7.55 (s, 1H, Ar), 7.70 (d, J=7.7 Hz, 1H, Ar), 8.16 (dd, J=2.5, 8.7 Hz, 1H, Ar), 8.71 (d, J=2.3 Hz, 1H, Ar), 9.14 (t, J=5.9 Hz, 1H, NH), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 14.40, 22.49, 31.20, 42.60, 47.12, 51.58, 61.80, 110.19, 122.07, 122.94, 123.26, 127.07, 130.39, 138.18, 142.40, 143.80, 147.10, 164.61, 164.91, 167.92, 170.98, 172.85; LCMS: MH=423; Anal Calcd for C22H22N4O5: C, 62.55; H, 5.25; N, 13.26. Found: C, 62.24; H, 5.19; N, 13.15.

Aufarbeitung

  1. temperaturethe mixture was heated at 50° C. for 1.5 h
  2. temperatureThe mixture was cooled to rt
  3. customThe solids were isolated by filtration
  4. customtriturated in EtOAc (20 mL) for 18 h
  5. filtrationThe product was filtered
  6. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-6133f6b9c30d4fd084995b138bf2c5ef
Quelldatensatz
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08877780B2

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion