Cesium carbonate → 1-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-one

HRID 2199887Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2199887
[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[N:13][CH:14]=[C:15](Br)[CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:19])=[CH:5][CH:4]=1.Cl.[NH:23]1[CH2:26][CH:25]([OH:27])[CH2:24]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([N:23]4[CH2:26][CH:25]([OH:27])[CH2:24]4)[CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:19])=[CH:5][CH:4]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 27592903-Hydroxyazetidine hydrochlorideHCID 679930111-(4-methoxybenzyl)-7-bromo-1,5-naphthyridin-2(1H)-one

Produkt 1

HCID 679929881-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-oneAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of 1-(4-methoxybenzyl)-7-bromo-1,5-naphthyridin-2(1H)-one (C-5) (8.1 g, 23.46 mmol, 1.0 eq), azetidin-3-ol hydrochloride (3.08 g, 28.15 mmol, 1.2 eq), Pd2(dba)3 (429 mg, 0.47 mmol, 0.02 eq), Xantphos (407 mg, 0.7 mmol, 0.03 eq) and Cs2CO3 (19.87 g, 61 mmol, 2.6 eq) in 1,4-dioxane (100 mL) was heated at reflux temperature under argon atmosphere overnight then cooled and filtered, the filter cake was washed with ethyl acetate and the combined filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (1-5% MeOH-DCM) to afford 1-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-one (C-6) (7.2 g, 91% yield). 1H NMR (300 MHz, DMSO-d6) δ: 7.76 (m, 2H), 7.17 (d, J=8.7 Hz, 2H), 6.84 (d, J=8.7 Hz, 2H), 8.53 (m, 2H), 5.68 (d, J=6.3 Hz, 1H), 5.34 (s, 2H), 4.56 (m, 1H), 4.13 (m, 2H), 3.66 (s, 3H), 3.59 (m, 2H); ESI-MS m/z: 338.1 [M+H]+.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux temperature under argon atmosphere overnight
  3. temperaturethen cooled
  4. filtrationfiltered
  5. washthe filter cake was washed with ethyl acetate
  6. concentrationthe combined filtrate was concentrated in vacuo
  7. customthe residue was purified by column chromatography on silica gel (1-5% MeOH-DCM)

Quellen und Nachweise

ORD-Eintrag
ord-03e19b42c381455ebe3697e532b3ffc8
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09359352B2

Notizen zur Reaktion

Wird geladen…