Cesium carbonate → Methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

HRID 1755347Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1755347
Br[C:2]1[C:3]2[N:4]([CH:18]=[CH:19][N:20]=2)[N:5]=[C:6]([C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=2)[C:11]([O:13][CH3:14])=[O:12])[CH:7]=1.[CH3:21][O:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:29]1[N:34]=[C:33]([NH2:35])[CH:32]=[CH:31][CH:30]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=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]>[CH3:21][O:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:29]1[N:34]=[C:33]([NH:35][C:2]2[C:3]3[N:4]([CH:18]=[CH:19][N:20]=3)[N:5]=[C:6]([C:8]3[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=3)[C:11]([O:13][CH3:14])=[O:12])[CH:7]=2)[CH:32]=[CH:31][CH:30]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86682703HCID 86682703, VerbindungHCID 866827206-(2-(Methoxymethyl)pyrrolidin-1-yl)pyridin-2-amine

Produkt 1

HCID 86682721Methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoateAusbeute 36,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of methyl 3-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate (0.10 g, 0.3 mmol), 6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-amine (0.083 g, 0.4 mmol), Pd2(dba)3 (0.019 g, 0.033 mmol), BINAP (0.083 g, 0.134 mmol) and Cs2CO3 (0.326 g, 1.0 mmol) in dioxane (20 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (0.050 g) as a yellow solid. LC-MS: [M+1]+=459, tR=1.985 min. This contained some unidentified impurities and was used directly without further purification.

Aufarbeitung

  1. concentrationthen concentrated in vacuo
  2. customThe residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15)

Quellen und Nachweise

ORD-Eintrag
ord-0985f44236c940068ecdfce53bba94e7
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169259B2

Notizen zur Reaktion

Wird geladen…