Sodium Carbonate → (R)-8-cyclopentyl-2-(2-(3,6-dihydro-2H-pyran-4-yl)-1H-imidazol-1-yl)-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

HRID 44848Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 44848
Br[C:2]1[N:3]([C:7]2[N:16]=[CH:15][C:14]3[N:13]([CH3:17])[C:12](=[O:18])[C@@H:11]([CH2:19][CH3:20])[N:10]([CH:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[C:9]=3[N:8]=2)[CH:4]=[CH:5][N:6]=1.C([O-])([O-])=O.[Na+].[Na+].[O:32]1[CH2:37][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH2:34][CH2:33]1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CO.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:21]1([N:10]2[C:9]3[N:8]=[C:7]([N:3]4[CH:4]=[CH:5][N:6]=[C:2]4[C:35]4[CH2:36][CH2:37][O:32][CH2:33][CH:34]=4)[N:16]=[CH:15][C:14]=3[N:13]([CH3:17])[C:12](=[O:18])[C@H:11]2[CH2:19][CH3:20])[CH2:25][CH2:24][CH2:23][CH2:22]1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 58405307(R)-2-(2-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

Produkt 1

HCID 58405609(R)-8-cyclopentyl-2-(2-(3,6-dihydro-2H-pyran-4-yl)-1H-imidazol-1-yl)-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 22592949Dioxane methanol waterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

(R)-2-(2-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one (Example 65, 130 mg, 1 eq) in dioxane/water/MeOH (2 mL/0.5 mL/0.05 mL) was combined with Pd(dppf)Cl2 (39.6 mg, 0.2 eq), Na2CO3 (100 mg, 3 eq), and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (116 mg, 2 eq). The reaction mixture was stirred at 110° C. overnight. This was diluted with EtOAc and a saturated NaHCO3 solution. The layers were separated and the aqueous layer was extracted with EtOAc (2×25 mL). The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by MPLC and further purified by preparative HPLC. LCMS: 409.2 m/z (M+H)+; ret. Time: 2.41 min (Analytical Method A). 1H-NMR (CDCl3, 300 MHz): δ: 7.81 (s, 1H), 7.67 (s, 1H), 7.46 (s, 1H), 6.51 (s, 1H), 4.35-4.30 (m, 4H), 3.90-3.81 (m, 4H), 3.40 (s, 3H), 2.41-2.3 (m, 1H), 2.20-1.54 (m, 9H), 0.89 (t, J=7.5 Hz, 3H).

Aufarbeitung

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by MPLC
  7. customfurther purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-194898befb5b4e6daf7fbcba96a62761
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541418B2

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