Cesium carbonate → 2-[2-(2-Hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

HRID 1922797

Reaktionsgleichung

Reaktionsgleichung von HRID 1922797
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:12]=[O:13])[N:8]2[CH3:11])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:3]=1.[NH:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=[C:21]1[CH2:29][CH2:30][OH:31].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.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]>[OH:31][CH2:30][CH2:29][C:21]1[N:20]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH:12]=[O:13])[N:8]3[CH3:11])=[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:3]=2)[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 785702-(Hydroxyethyl)benzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596034722-Chloro-9-methyl-6-morpholino-9H-purine-8-carbaldehyde

Produkt 1

HCID 596052312-[2-(2-Hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehydeAusbeute 67,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Versuchsvorschrift

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (500 mg, 1.78 mmol), 2-(1H-benzoimidazol-2-yl)ethanol (335 mg, 2.06 mmol), Pd2dba3 (40 mg, 0.043 mmol), Xphos (85 mg, 0.18 mmol) and cesium carbonate (840 mg, 2.58 mmol) in 1,4-dioxane (10 mL) was purged with argon gas then subjected to microwave irradiation at 145° C. for 30 min. The reaction mixture was filtered through a pad of Celite® and the filtrate was concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, EtOAc: MeOH; 100:0 to 98:2 to 95:5 to 90:10) to afford 2-[2-(2-Hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde as a yellow solid (487 mg, 67%). 1H NMR (CDCl3, 400MHz) 6 9.93 (s, 1 H); 8.16-8.12 (m, 1 H); 7.76-7.72 (m, 1 H); 7.35-7.29 (m, 2 H); 4.52 (m, 4 H); 4.20 (t, J=5.3 Hz, 2 H); 4.14 (s, 3 H); 3.91 (m, 5 H) and 3.57 (t, J=5.3 Hz, 2 H).

Aufarbeitung

  1. customwas purged with argon gas
  2. customirradiation at 145° C. for 30 min
  3. filtrationThe reaction mixture was filtered through a pad of Celite®
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, EtOAc: MeOH; 100:0 to 98:2 to 95:5 to 90:10)

Quellen und Nachweise

ORD-Eintrag
ord-29b055d0132b44d3a8958bc64591300e
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

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