Dimethyl Sulfoxide → Gsk-256073

HRID 1943795Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1943795
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[NH:7][C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1.CS(C)=O.N1CCOCC1>C1COCC1.CCOC(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:14])[NH:7][C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1

Komponenten

7

Edukt 3

HCID 679Dimethyl SulfoxideHCID 8083MorpholineHCID 592995577-Allyl-8-chloro-3-pentyl-1H-purine-2,6(3H,7H)-dione

Produkt 1

HCID 46215799Gsk-256073Ausbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A flask containing tetrakis(triphenylphosphine)-palladium (0) (56 mg, 0.049 mmol) was flushed with nitrogen, before a solution of 8-chloro-3-pentyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (96 mg, 0.323 mmol) in anhydrous THF (1.5 ml) was added, followed by DMSO (0.1 ml) and morpholine (0.28 ml, 0.049 mmol). The resulting mixture was stirred at room temperature under nitrogen for 72 hours. The reaction mixture was dissolved in EtOAc (25 ml) and washed with 2M HCl aq. (25 ml). The organic extract was dried (MgSO4) filtered and evaporated under reduced pressure. Purification by amino propyl SPE (2 g) loading and washing with methanol and then eluting the product with 5% acetic acid in methanol. Evaporation of fractions containing product afforded the title compound as a white solid (27 mg, 33%). NMR; δH (400 MHz, d6-DMSO) 0.85 (t, 3H, J=7 Hz), 1.20-1.34 (m, 4H), 1.57-1.67 (m, 2H), 3.84 (t, 2H, J=7 Hz), 11.19 (s, 1H), 14.38 (br. s, 1H); m/z 257.2[MH+].

Aufarbeitung

  1. additionwas added
  2. washwashed with 2M HCl aq. (25 ml)
  3. extractionThe organic extract
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customPurification by amino propyl SPE (2 g) loading
  8. washwashing with methanol
  9. washeluting the product with 5% acetic acid in methanol
  10. customEvaporation of fractions
  11. additioncontaining product

Quellen und Nachweise

ORD-Eintrag
ord-45cd9eaf5e6e40bd9506daaf70fad95a
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08394808B2

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