Diisopropylethylamine → HCID 178463182, compound

Participants

Reaction Conditions

Reaction Steps

(2R,3R,4R,5R)-2-(2-Chloro-6-{[trans-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)cyclohexyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydrofuran-3,4-diyl diacetate (Intermediate 1) (5.2 mmol) was treated with 1:1 trifluoroacetic acid/dichloromethane (20 ml) for ca. 2 h. This was concentrated in vacuo and the residue was purified by SPE (SCX, 50 g), eluting sequentially with dichloromethane, methanol, 40% (2M ammonia in methanol): dichloromethane and 2M ammonia in methanol. The appropriate fraction was concentrated in vacuo and suspended in propan-2-ol (60 ml). To this was added N,N-diisopropylethylamine (4 m. eq.) and 2,6-dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (prepared according to the method disclosed in WO2003080604A1) (1 m. eq.) and this was heated at 60° C. overnight. After cooling to room temperature, further 2,6-dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (0.5 m. eq.) and N,N-diisopropylethylamine (4 ml) were added and this was heated at 60° C. for a further ca. 5 h. After cooling to room temperature, the reaction mixture was then concentrated in vacuo and the residue was partitioned between dichloromethane (ca. 60 ml) and water (ca. 60 ml). The organics were washed with water (ca. 60 ml), dried over magnesium sulfate and concentrated in vacuo to yield the title compound as an off-white crystalline solid, 4 g.

Provenance & Evidence