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 (for example, as prepared for Intermediate 6) (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. The reaction mixture was then cooled to room temperature and to this was added phenylmethyl 3-(bromomethyl)-1-piperidinecarboxylate (commercially available, for example, from AniChem, or for a prep see International Patent Application Publication Number WO1999/45006) (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. temperatureThe reaction mixture was then cooled to room temperature
3. customwas bought back up to 50° C.
4. waitleft
5. stirringto stir overnight
6. custompartitioned with a solvent
7. additionmix of 1:1 ethyl acetate
8. customThe organic layer was separated
9. concentrationwas concentrated in vacuo
10. customto give pale yellow thick oil
11. customMeOH (5 mL) and half of this solution was initially purified on reverse phase chromatography

ORD-Eintrag

ord-ab210c16f3154898aaad91f7a05cd06a

Quelldatensatz

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08575340B2