Cesium carbonate → 2-(1-(2-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)ethyl)piperidin-4-yl)propan-2-ol

HRID 1923097Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1923097
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][CH:17]([C:20]([OH:23])([CH3:22])[CH3:21])[CH2:16][CH2:15]3)[N:8]2[CH3:11])=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:3]=1.[CH2:30]([C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31].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]>[CH2:30]([C:32]1[N:33]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]4[CH2:15][CH2:16][CH:17]([C:20]([OH:23])([CH3:21])[CH3:22])[CH2:18][CH2:19]4)[N:8]3[CH3:11])=[C:4]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[N:3]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596057382-{1-[2-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]piperidin-4-yl}propan-2-ol

Produkt 1

HCID 596061302-(1-(2-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)ethyl)piperidin-4-yl)propan-2-olAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 2-{1-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-piperidin-4-yl}propan-2-ol (71 mg, 0.17 mmol), 2-ethylbenzimidazole (27 mg, 0.19 mmol), Pd2(dba)3 (3.8 mg, 2.5 mol %), Xphos (8.0 mg, 10 mol %) and Cs2CO3 (82 mg, 0.25 mmol) in dioxane (1 0 mL) was purged with argon gas then heated at 120° C., for 19 h, in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PCC, 0-10% MeOH in DCM) to give 367 (45 mg, 50%) as a yellow solid. LCMS: (Method G): RT 6.09 min; [M+H]+ 533.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.97 (m, 1 H), 7.77-7.72 (m, 1 H), 7.29-7.23 (m, 2 H), 4.49-4.15 (m, 4H), 3.88-3.83 (m, 4 H), 3.78 (s, 3 H), 3.34 (q, J=7.5, 2 H), 3.14 (m, 4 H), 2.93-2.75 (m, 2H), 2.20-2.08 (m, 2 H), 1.85-1.78 (m, 2 H), 1.44 (t, J=7.5 Hz, 3 H), 1.40-1.21 (m, 3 H), 1.24-1.18 (m, 6 H)

Aufarbeitung

  1. customwas purged with argon gas
  2. washwashed with MeOH
  3. washthe desired product eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by flash chromatography (Si—PCC, 0-10% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-3ebffc01711f407da3441a555e736115
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

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