Morpholine → 5-(8-chloro-2,6-dioxo-3-pentyl-2,3,6,7-tetrahydro-1H-purin-1-yl)pentanenitrile

Temperatur

50 °C

A solution of 8-chloro-3-pentyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (4.0 g, 13.5 mmol) in DMF (100 ml) was treated with caesium carbonate (4.83 g, 14.8 mmol) and 5-bromopentanenitrile (1.73 ml, 14.8 mmol). The mixture was heated at 50° C. in a nitrogen atmosphere for 19 h and then cooled. The mixture was then degassed by the repeated successive application of a vacuum and then nitrogen pressure. The mixture was then treated with tetrakis(triphenylphosphine)palladium(0) (1.1 g, 0.94 mmol) and morpholine (11.8 ml, 136 mmol). The mixture was stirred in a nitrogen atmosphere for 3 h and then partitioned between EtOAc and 2M aqueous hydrochloric acid. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated to reveal a yellow, oily residue. This was dissolved in MeOH, divided equally into four portions and each portion applied to a 20 g aminopropyl SPE which was then washed through with MeOH. The desired product was eluted from the cartridge with a 5% v/v solution of AcOH in MeOH. The product-containing fractions were combined and concentrated to yield the title compound as a pale yellow solid (4.03 g, 88%).

1. temperaturecooled
2. customThe mixture was then degassed by the repeated successive application of a vacuum
3. custompartitioned between EtOAc and 2M aqueous hydrochloric acid
4. customThe organic layer was separated
5. washwashed with brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrated
8. dissolutionThis was dissolved in MeOH
9. washwas then washed through with MeOH
10. washThe desired product was eluted from the cartridge with a 5% v/v solution of AcOH in MeOH
11. concentrationconcentrated

ORD-Eintrag

ord-4d026ecfdac44180a307ee757dd82cac

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08143264B2