Potassium Carbonate → (2-{6-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-2-phenyl-ethyl)-carbamic acid tert-butyl ester

HRID 1186508Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1186508
Br[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][N:15]=[C:16]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1.[C:24]([O:28][C:29](=[O:40])[NH:30][CH2:31][CH:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([CH3:27])([CH3:26])[CH3:25].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C([O-])([O-])=O.[K+].[K+]>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]>[C:24]([O:28][C:29](=[O:40])[NH:30][CH2:31][CH:32]([NH:39][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][N:15]=[C:16]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:11]3=[N:10][CH:9]=2)[N:7]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)([CH3:27])([CH3:25])[CH3:26]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 2771847tert-butyl N-(2-amino-2-phenylethyl)carbamateHCID 86670919HCID 86670919, Verbindung

Produkt 1

HCID 68226762(2-{6-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-2-phenyl-ethyl)-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of 3-(6-bromo-pyridin-2-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine (from Example 39 supra) (0.56 g, 1.5 mmol), (2-amino-2-phenyl-ethyl)-carbamic acid tert-butyl ester (from Example 51 supra) (0.425 g, 1.8 mmol), Pd2(dba)3 (90 mg), Davephos (120 mg), K2CO3 (0.25 g, 1.8 mmol) in dioxane (40 mL) in a sealed tube was bubbled with N2 for several minutes and then heated under N2 at 130° C. overnight. The mixture was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was first purified by chromatography (CH2Cl2:CH3OH, 100:1), then by preparative-HPLC to give (2-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-ylamino}-2-phenyl-ethyl)-carbamic acid tert-butyl ester. (Yield 30 mg, 3.8%). LC-MS: [M+H]+ 529.

Aufarbeitung

  1. customwas bubbled with N2 for several minutes
  2. temperatureThe mixture was then cooled to room temperature
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was first purified by chromatography (CH2Cl2:CH3OH, 100:1)

Quellen und Nachweise

ORD-Eintrag
ord-b11c82af1cde4f29ad9020c15dafeda3
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673905B2

Notizen zur Reaktion

Wird geladen…