Cesium carbonate → 4-(8-((4-(2-methoxypropan-2-yl)piperidin-1-yl)methyl)-9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-9H-purin-6-yl)morpholine

HRID 1922943Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1922943
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+].Cl[C:42]1[N:50]=[C:49]2[C:45]([N:46]=[C:47]([CH2:52][N:53]3[CH2:58][CH2:57][CH:56]([C:59]([O:62][CH3:63])([CH3:61])[CH3:60])[CH2:55][CH2:54]3)[N:48]2[CH3:51])=[C:44]([N:64]2[CH2:69][CH2:68][O:67][CH2:66][CH2:65]2)[N:43]=1.[CH3:70][C:71]1[NH:75][C:74]2[CH:76]=[CH:77][CH:78]=[CH:79][C:73]=2[N:72]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:63][O:62][C:59]([CH:56]1[CH2:57][CH2:58][N:53]([CH2:52][C:47]2[N:48]([CH3:51])[C:49]3[C:45]([N:46]=2)=[C:44]([N:64]2[CH2:65][CH2:66][O:67][CH2:68][CH2:69]2)[N:43]=[C:42]([N:72]2[C:73]4[CH:79]=[CH:78][CH:77]=[CH:76][C:74]=4[N:75]=[C:71]2[CH3:70])[N:50]=3)[CH2:54][CH2:55]1)([CH3:60])[CH3:61]

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 119842-MethylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596057264-(2-chloro-8-((4-(2-methoxypropan-2-yl)piperidin-1-yl)methyl)-9-methyl-9H-purin-6-yl)morpholine

Produkt 1

HCID 596055814-(8-((4-(2-methoxypropan-2-yl)piperidin-1-yl)methyl)-9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-9H-purin-6-yl)morpholine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

Alternatively, following General Procedure I, one-step Buchwald coupling, a microwave tube was charged with Xphos (0.1 equiv.), tris(dibenzylideneacetone)dipalladium(0) (0.05 equiv.), cesium carbonate (2 equiv.), 4-(2-chloro-8-((4-(2-methoxypropan-2-yl)piperidin-1-yl)methyl)-9-methyl-9H-purin-6-yl)morpholine (80 mg, 1 equiv.) and 2-methyl-1H-benzo[d]imidazole (1.2 equiv.). The vessel is evacuated and refilled with nitrogen prior to the addition of DMF or 1,4-dioxane. The mixture is heated in a microwave device, such as Biotage at about 140° C. for about 25-35 minutes. The reaction mixture is cooled to room temperature, filtered and concentrated, and purified by RP-HPLC to give 17.1 mg of 179. MS (Q1) 519.1 (M)+.

Aufarbeitung

  1. customThe vessel is evacuated
  2. additionrefilled with nitrogen
  3. additionto the addition of DMF or 1,4-dioxane
  4. temperatureThe reaction mixture is cooled to room temperature
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by RP-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-48a2c6c43c77469fa40b26cd0b000416
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

Notizen zur Reaktion

Wird geladen…