Hydrochloric Acid → Ethyl 4-(3-butyl-8-chloro-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)butanoate

HRID 1097657Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1097657
[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[N:10](CC=C)[C:9]=2[C:8](=[O:18])[NH:7][C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:27][CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31].N1CCOCC1.Cl>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CCOC(C)=O>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([Cl:14])[NH:10][C:9]=2[C:8](=[O:18])[N:7]([CH2:27][CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 10796Cesium carbonateHCID 76300Ethyl 4-bromobutyrateHCID 592995823-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione

Produkt 1

HCID 59395861Ethyl 4-(3-butyl-8-chloro-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)butanoateAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

To 3-butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (6.0 g, 21.24 mmol) in dry DMF (100 ml) was added Cs2CO3 (7.62 g, 23.36 mmol) followed by ethyl 4-bromobutyrate (4.556 g, 23.36 mmol). The mixture was heated at 55° C. for 18 h and allowed to cool then degassed by repeatedly evacuating and readmitting nitrogen. Morpholine (14.9 g, 171 mmol) was added followed by tetrakis(triphenylphosphine)palladium(0) (4.0 g, 3.46 mmol) and the mixture was stirred for 4 h. EtOAc (300 ml) and 2M HCl (150 ml) and water (100 ml) were added and the organic phase separated, washed with brine (3×100 ml) and filtered. The filtrate was dried (Na2SO4) and evaporated. The crude product (10 g) was purified by aminopropyl SPE (3×20 g), loading in THF/MeOH (1:1), washing with THF/MeOH (1:1) and neat MeOH and eluting the product with DCM/MeOH (1:1) containing 5% added AcOH to afford the title compound (5.08 g).

Aufarbeitung

  1. temperatureto cool
  2. customthen degassed
  3. customby repeatedly evacuating
  4. customthe organic phase separated
  5. washwashed with brine (3×100 ml)
  6. filtrationfiltered
  7. dry with materialThe filtrate was dried (Na2SO4)
  8. customevaporated
  9. customThe crude product (10 g) was purified by aminopropyl SPE (3×20 g)
  10. washwashing with THF/MeOH (1:1) and neat MeOH
  11. washeluting the product with DCM/MeOH (1:1)
  12. additioncontaining 5%
  13. additionadded AcOH

Quellen und Nachweise

ORD-Eintrag
ord-72876a317d6049c48acfd8e748bcabc3
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143264B2

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