Potassium Carbonate → Phenylmethyl 3-{[6-amino-2-(butyloxy)-8-(methyloxy)-9H-purin-9-yl]methyl}-1-piperidinecarboxylate

Temperatur

60 °C

To a solution of 2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine. trifluoroacetate salt (2.56 g, 7.29 mmol) in DMF (60 ml) was added potassium carbonate (4.03 g, 29.1 mmol) and the mixture was left to stir at 60° C. for one hour under an atmosphere of nitrogen. Reaction was then cooled to room temperature and to this was added phenylmethyl 3-(bromomethyl)-1-piperidinecarboxylate (2.275 g, 7.29 mmol). The reaction was bought back up to 50° C. and left to stir overnight. The reaction mixture was diluted with water (˜40 ml) and partitioned with a solvent mix of 1:1 ethyl acetate:DCM (40 ml). The organic layer was separated using hydrophobic frit and was concentrated in vacuo to give pale yellow thick oil. The crude material was dissolved in 1:1 DMSO:MeOH (5 ml) and half of this solution was initially purified on reverse-phase chromatography using a high pH system on a 330 g C18 silica column. The gradient used was the following:

1. waitthe mixture was left
2. customReaction
3. temperaturewas then cooled to room temperature
4. customwas bought back up to 50° C.
5. waitleft
6. stirringto stir overnight
7. custompartitioned with a solvent
8. additionmix of 1:1 ethyl acetate
9. customThe organic layer was separated
10. concentrationwas concentrated in vacuo
11. customto give pale yellow thick oil
12. customMeOH (5 ml) and half of this solution was initially purified on reverse-phase chromatography

ORD-Eintrag

ord-86ec9434238d45eb960cf9c5659ed5ad

Quelldatensatz

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08802684B2